{"topic":"cancer-immunotherapy","sort":"top","limit":25,"offset":0,"count":25,"papers":[{"id":"doi:10.1159/000455014","kind":"review","title":"Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review","authors":["Rimda Wanchoo","Sabine Karam","Nupur N. Uppal","Valerie S. Barta","Gilbert Deray","Craig Devoe","Vincent Launay‐Vacher","Kenar D. Jhaveri","on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors"],"author_count":9,"year":2017,"published":"2017-01-01","venue":"American Journal of Nephrology","cited_by":15256,"doi":"10.1159/000455014","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1159/000455014","archive_url":"https://space-kitty.com/papers/doi:10.1159/000455014","updated":null,"pmid":"28076863","pmcid":null,"openalex_id":"W2572174216","pdf_url":"https://www.karger.com/Article/Pdf/455014","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Cancer Immunotherapy and Biomarkers"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41572-020-00240-3","kind":"review","title":"Hepatocellular carcinoma","authors":["Josep Maria Llovet","Robin Kate Kelley","Augusto Villanueva","Amit G. Singal","Eli Pikarsky","Sasan Roayaie","Riccardo Antonio Lencioni","Kazuhiko Koike","Jessica Zucman‐Rossi","Richard S. Finn"],"author_count":10,"year":2021,"published":"2021-01-21","venue":"Nature Reviews Disease Primers","cited_by":7050,"doi":"10.1038/s41572-020-00240-3","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41572-020-00240-3","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41572-020-00240-3","updated":null,"pmid":"33479224","pmcid":null,"openalex_id":"W4210774372","pdf_url":"https://www.nature.com/articles/s41572-020-00240-3.pdf","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Hepatocellular Carcinoma Treatment and Prognosis"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41588-018-0312-8","kind":"article","title":"Tumor mutational load predicts survival after immunotherapy across multiple cancer types","authors":["Robert M. Samstein","Chung‐Han Lee","Alexander Noor Shoushtari","Matthew David Hellmann","Ronglai Shen","Yelena Yuriy Janjigian","David A. Barron","Ahmet Zehir","Emmet Jordan","Antonio M. P. Omuro","Thomas Joseph Kaley","Sviatoslav M. Kendall","Robert John Motzer","A. Ari Hakimi","Martin Henner Voss","Paul Russo","Jonathan E. Rosenberg","Gopa Iyer","Bernard H. Bochner","Dean F. Bajorin","Hikmat A Al‐Ahmadie","Jamie E. Chaft","Charles M. Rudin","Gregory J. Riely","Shrujal S. Baxi"],"author_count":57,"year":2019,"published":"2019-01-08","venue":"Nature Genetics","cited_by":4069,"doi":"10.1038/s41588-018-0312-8","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41588-018-0312-8","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41588-018-0312-8","updated":null,"pmid":"30643254","pmcid":null,"openalex_id":"W2909679049","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Cancer Immunotherapy and Biomarkers"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1186/s13073-017-0424-2","kind":"article","title":"Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden","authors":["Zachary Rockow Chalmers","Caitlin F. Connelly","David A. Fabrizio","Laurie M. Gay","Siraj Mahamed Ali","Riley Charles Ennis","Alexa Betzig Schrock","Brittany B. Campbell","Adam Shlien","Juliann Chmielecki","Franklin W. Huang","Yuting He","James Sun","Uri Y. Tabori","Mark Kennedy","Daniel S. Lieber","Steven M. Roels","Jared R. White","Geoff A. Otto","Jeffrey S. Ross","Levi A. Garraway","Vincent A. Miller","Phillip J. Stephens","Garrett Michael Frampton"],"author_count":24,"year":2017,"published":"2017-04-13","venue":"Genome Medicine","cited_by":3517,"doi":"10.1186/s13073-017-0424-2","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1186/s13073-017-0424-2","archive_url":"https://space-kitty.com/papers/doi:10.1186/s13073-017-0424-2","updated":null,"pmid":"28420421","pmcid":null,"openalex_id":"W2606495925","pdf_url":"https://genomemedicine.biomedcentral.com/counter/pdf/10.1186/s13073-017-0424-2","abstract":"BACKGROUND: High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors and has been shown to be more significantly associated with response to PD-1 and PD-L1 blockade immunotherapy than PD-1 or PD-L1 expression, as measured by immunohistochemistry (IHC). The distribution of TMB and the subset of patients with high TMB has not been well characterized in the majority of cancer types. METHODS: In this study, we compare TMB measured by a targeted comprehensive genomic profiling (CGP) assay to TMB measured by exome sequencing and simulate the expected variance in TMB when sequencing less than the whole exome. We then describe the distribution of TMB across a diverse cohort of 100,000 cancer cases and test for association between somatic alterations and TMB in over 100 tumor types. RESULTS: We demonstrate that measurements of TMB from comprehensive genomic profiling are strongly reflective of measurements from whole exome sequencing and model that below 0.5 Mb the variance in measurement increases significantly. We find that a subset of patients exhibits high TMB across almost all types of cancer, including many rare tumor types, and characterize the relationship between high TMB and microsatellite instability status. We find that TMB increases significantly with age, showing a 2.4-fold difference between age 10 and age 90 years. Finally, we investigate the molecular basis of TMB and identify genes and mutations associated with TMB level. We identify a cluster of somatic mutations in the promoter of the gene PMS2, which occur in 10% of skin cancers and are highly associated with increased TMB. CONCLUSIONS: These results show that a CGP assay targeting ~1.1 Mb of coding genome can accurately assess TMB compared with sequencing the whole exome. Using this method, we find that many disease types have a substantial portion of patients with high TMB who might benefit from immunotherapy. Finally, we identify novel, recurrent promoter mutations in PMS2, which may be another example of regulatory mutations contributing to tumorigenesis.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Cancer Immunotherapy and Biomarkers"],"details":null,"provenance":"openalex","attribution":"Abstract of \"Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden\" by Zachary Rockow Chalmers, Caitlin F. Connelly, David A. Fabrizio et al., https://doi.org/10.1186/s13073-017-0424-2, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1038/s41423-020-0488-6","kind":"review","title":"The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications","authors":["Yuanyuan Zhang","Zemin Zhang"],"author_count":2,"year":2020,"published":"2020-07-01","venue":"Cellular and Molecular Immunology","cited_by":2817,"doi":"10.1038/s41423-020-0488-6","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41423-020-0488-6","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41423-020-0488-6","updated":null,"pmid":"32612154","pmcid":null,"openalex_id":"W3039484069","pdf_url":"https://www.nature.com/articles/s41423-020-0488-6.pdf","abstract":"Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology. Several types of immunotherapy, including adoptive cell transfer (ACT) and immune checkpoint inhibitors (ICIs), have obtained durable clinical responses, but their efficacies vary, and only subsets of cancer patients can benefit from them. Immune infiltrates in the tumor microenvironment (TME) have been shown to play a key role in tumor development and will affect the clinical outcomes of cancer patients. Comprehensive profiling of tumor-infiltrating immune cells would shed light on the mechanisms of cancer-immune evasion, thus providing opportunities for the development of novel therapeutic strategies. However, the highly heterogeneous and dynamic nature of the TME impedes the precise dissection of intratumoral immune cells. With recent advances in single-cell technologies such as single-cell RNA sequencing (scRNA-seq) and mass cytometry, systematic interrogation of the TME is feasible and will provide insights into the functional diversities of tumor-infiltrating immune cells. In this review, we outline the recent progress in cancer immunotherapy, particularly by focusing on landmark studies and the recent single-cell characterization of tumor-associated immune cells, and we summarize the phenotypic diversities of intratumoral immune cells and their connections with cancer immunotherapy. We believe such a review could strengthen our understanding of the progress in cancer immunotherapy, facilitate the elucidation of immune cell modulation in tumor progression, and thus guide the development of novel immunotherapies for cancer treatment.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Cancer Immunotherapy and Biomarkers"],"details":null,"provenance":"openalex","attribution":"Abstract of \"The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications\" by Yuanyuan Zhang, Zemin Zhang, https://doi.org/10.1038/s41423-020-0488-6, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1038/nrclinonc.2016.66","kind":"review","title":"Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease","authors":["Giampaolo Bianchini","Justin Micah Balko","Ingrid A. Mayer","Melinda E. Sanders","Luca Gianni"],"author_count":5,"year":2016,"published":"2016-05-17","venue":"Nature Reviews Clinical Oncology","cited_by":3073,"doi":"10.1038/nrclinonc.2016.66","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/nrclinonc.2016.66","archive_url":"https://space-kitty.com/papers/doi:10.1038/nrclinonc.2016.66","updated":null,"pmid":"27184417","pmcid":null,"openalex_id":"W2402636472","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Breast Cancer Treatment Studies"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41392-022-00947-7","kind":"review","title":"Antibody drug conjugate: the \"biological missile\" for targeted cancer therapy","authors":["Fu Z","Li S","Han S","Shi C","Zhang Y"],"author_count":5,"year":2022,"published":"2022-03-22","venue":"Signal transduction and targeted therapy","cited_by":1271,"doi":"10.1038/s41392-022-00947-7","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41392-022-00947-7","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41392-022-00947-7","updated":null,"pmid":"35318309","pmcid":"PMC8941077","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC8941077/pdf","abstract":"Antibody-drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a chemical linker. It combines both the advantages of highly specific targeting ability and highly potent killing effect to achieve accurate and efficient elimination of cancer cells, which has become one of the hotspots for the research and development of anticancer drugs. Since the first ADC, Mylotarg ® (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA), there have been 14 ADCs received market approval so far worldwide. Moreover, over 100 ADC candidates have been investigated in clinical stages at present. This kind of new anti-cancer drugs, known as \"biological missiles\", is leading a new era of targeted cancer therapy. Herein, we conducted a review of the history and general mechanism of action of ADCs, and then briefly discussed the molecular aspects of key components of ADCs and the mechanisms by which these key factors influence the activities of ADCs. Moreover, we also reviewed the approved ADCs and other promising candidates in phase-3 clinical trials and discuss the current challenges and future perspectives for the development of next generations, which provide insights for the research and development of novel cancer therapeutics using ADCs.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Antibody drug conjugate: the \"biological missile\" for targeted cancer therapy\" by Fu Z, Li S, Han S et al., https://doi.org/10.1038/s41392-022-00947-7, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1186/s40425-017-0300-z","kind":"article","title":"Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group","authors":["on behalf of the Society for Immunotherapy of Cancer Toxicity Management Working Group","Igor J. Puzanov","Adi K. Diab","K. Abdallah","Clifton O. Bingham","Cynthia F. Brogdon","Ramona Dadu","Lamya Hamad","Sungjun Kim","Mario E. Lacouture","Nicole R. LeBoeuf","Daniel John Lenihan","C.D. Onofrei","Vickie R. Shannon","Rajeev Sharma","Ann Willman Silk","Dimitra Skondra","Maria Eugenia Suarez-Almazor","Yinghong Wang","K. Wiley","Howard L. Kaufman","Marc S. Ernstoff"],"author_count":22,"year":2017,"published":"2017-11-21","venue":"Journal for ImmunoTherapy of Cancer","cited_by":1992,"doi":"10.1186/s40425-017-0300-z","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1186/s40425-017-0300-z","archive_url":"https://space-kitty.com/papers/doi:10.1186/s40425-017-0300-z","updated":null,"pmid":"29162153","pmcid":"PMC5697162","openalex_id":"W2768429453","pdf_url":"https://jitc.bmj.com/content/jitc/5/1/95.full.pdf","abstract":"Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a discrete group of immune-related adverse events (irAEs). Many of these are driven by the same immunologic mechanisms responsible for the drugs' therapeutic effects, namely blockade of inhibitory mechanisms that suppress the immune system and protect body tissues from an unconstrained acute or chronic immune response. Skin, gut, endocrine, lung and musculoskeletal irAEs are relatively common, whereas cardiovascular, hematologic, renal, neurologic and ophthalmologic irAEs occur much less frequently. The majority of irAEs are mild to moderate in severity; however, serious and occasionally life-threatening irAEs are reported in the literature, and treatment-related deaths occur in up to 2% of patients, varying by ICI. Immunotherapy-related irAEs typically have a delayed onset and prolonged duration compared to adverse events from chemotherapy, and effective management depends on early recognition and prompt intervention with immune suppression and/or immunomodulatory strategies. There is an urgent need for multidisciplinary guidance reflecting broad-based perspectives on how to recognize, report and manage organ-specific toxicities until evidence-based data are available to inform clinical decision-making. The Society for Immunotherapy of Cancer (SITC) established a multidisciplinary Toxicity Management Working Group, which met for a full-day workshop to develop recommendations to standardize management of irAEs. Here we present their consensus recommendations on managing toxicities associated with immune checkpoint inhibitor therapy.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Cancer Immunotherapy and Biomarkers"],"details":null,"provenance":"openalex+europepmc","attribution":"Abstract of \"Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group\" by on behalf of the Society for Immunotherapy of Cancer Toxicity Management Working Group, Igor J. Puzanov, Adi K. Diab et al., https://doi.org/10.1186/s40425-017-0300-z, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1038/s12276-018-0191-1","kind":"review","title":"Immune checkpoint inhibitors: recent progress and potential biomarkers","authors":["Darvin P","Toor SM","Sasidharan Nair V","Elkord E"],"author_count":4,"year":2018,"published":"2018-12-13","venue":"Experimental & molecular medicine","cited_by":1602,"doi":"10.1038/s12276-018-0191-1","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s12276-018-0191-1","archive_url":"https://space-kitty.com/papers/doi:10.1038/s12276-018-0191-1","updated":null,"pmid":"30546008","pmcid":"PMC6292890","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC6292890/pdf","abstract":"Cancer growth and progression are associated with immune suppression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. Monoclonal antibodies that target immune checkpoints provided an immense breakthrough in cancer therapeutics. Among the immune checkpoint inhibitors, PD-1/PD-L1 and CTLA-4 inhibitors showed promising therapeutic outcomes, and some have been approved for certain cancer treatments, while others are under clinical trials. Recent reports have shown that patients with various malignancies benefit from immune checkpoint inhibitor treatment. However, mainstream initiation of immune checkpoint therapy to treat cancers is obstructed by the low response rate and immune-related adverse events in some cancer patients. This has given rise to the need for developing sets of biomarkers that predict the response to immune checkpoint blockade and immune-related adverse events. In this review, we discuss different predictive biomarkers for anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors, including immune cells, PD-L1 overexpression, neoantigens, and genetic and epigenetic signatures. Potential approaches for further developing highly reliable predictive biomarkers should facilitate patient selection for and decision-making related to immune checkpoint inhibitor-based therapies.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Immune checkpoint inhibitors: recent progress and potential biomarkers\" by Darvin P, Toor SM, Sasidharan Nair V et al., https://doi.org/10.1038/s12276-018-0191-1, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1038/nature23003","kind":"article","title":"Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer","authors":["Uğur Şahin","Evelyna Derhovanessian","Matthias Miller","Björn‐Philipp Kloke","Petra Simon","Martin Löwer","Valesca Bukur","Arbel D. Tadmor","Ulrich Luxemburger","Barbara Schrörs","Tana Omokoko","Mathias Vormehr","Christian H. Albrecht","Anna Paruzynski","Andreas N. Kuhn","Janina Buck","Sandra Heesch","Katharina H. Schreeb","Felicitas Müller","Inga Ortseifer","Isabel Vogler","Eva Godehardt","Sebastian Attig","Richard Rae","Andrea Breitkreuz"],"author_count":50,"year":2017,"published":"2017-07-04","venue":"Nature","cited_by":2485,"doi":"10.1038/nature23003","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/nature23003","archive_url":"https://space-kitty.com/papers/doi:10.1038/nature23003","updated":null,"pmid":"28678784","pmcid":null,"openalex_id":"W2724264513","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":["Immunotherapy and Immune Responses"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41568-019-0116-x","kind":"review","title":"The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy","authors":["Jonathan J. Havel","Diego Chowell","Timothy An-thy Chan"],"author_count":3,"year":2019,"published":"2019-02-12","venue":"Nature reviews. Cancer","cited_by":2285,"doi":"10.1038/s41568-019-0116-x","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41568-019-0116-x","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41568-019-0116-x","updated":null,"pmid":"30755690","pmcid":null,"openalex_id":"W2914335731","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Cancer Immunotherapy and Biomarkers"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1146/annurev-pathol-042020-042741","kind":"review","title":"Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance","authors":["Sreya Bagchi","Robert T. Yuan","Edgar G. Engleman"],"author_count":3,"year":2020,"published":"2020-11-16","venue":"Annual Review of Pathology Mechanisms of Disease","cited_by":2188,"doi":"10.1146/annurev-pathol-042020-042741","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1146/annurev-pathol-042020-042741","archive_url":"https://space-kitty.com/papers/doi:10.1146/annurev-pathol-042020-042741","updated":null,"pmid":"33197221","pmcid":null,"openalex_id":"W3106005610","pdf_url":"https://www.annualreviews.org/doi/pdf/10.1146/annurev-pathol-042020-042741","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Cancer Immunotherapy and Biomarkers"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41392-022-01046-3","kind":"review","title":"Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy","authors":["Weitong Gao","Yuqin Wang","Yang Zhou","Xueqian Wang","Yan Yu"],"author_count":5,"year":2022,"published":"2022-06-20","venue":"Signal Transduction and Targeted Therapy","cited_by":1052,"doi":"10.1038/s41392-022-01046-3","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41392-022-01046-3","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41392-022-01046-3","updated":null,"pmid":"35725836","pmcid":"PMC9208265","openalex_id":"W4283156085","pdf_url":"https://www.nature.com/articles/s41392-022-01046-3.pdf","abstract":"In recent years, immunotherapy represented by immune checkpoint inhibitors (ICIs) has led to unprecedented breakthroughs in cancer treatment. However, the fact that many tumors respond poorly or even not to ICIs, partly caused by the absence of tumor-infiltrating lymphocytes (TILs), significantly limits the application of ICIs. Converting these immune \"cold\" tumors into \"hot\" tumors that may respond to ICIs is an unsolved question in cancer immunotherapy. Since it is a general characteristic of cancers to resist apoptosis, induction of non-apoptotic regulated cell death (RCD) is emerging as a new cancer treatment strategy. Recently, several studies have revealed the interaction between non-apoptotic RCD and antitumor immunity. Specifically, autophagy, ferroptosis, pyroptosis, and necroptosis exhibit synergistic antitumor immune responses while possibly exerting inhibitory effects on antitumor immune responses. Thus, targeted therapies (inducers or inhibitors) against autophagy, ferroptosis, pyroptosis, and necroptosis in combination with immunotherapy may exert potent antitumor activity, even in tumors resistant to ICIs. This review summarizes the multilevel relationship between antitumor immunity and non-apoptotic RCD, including autophagy, ferroptosis, pyroptosis, and necroptosis, and the potential targeting application of non-apoptotic RCD to improve the efficacy of immunotherapy in malignancy.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Ferroptosis and cancer prognosis"],"details":null,"provenance":"openalex+europepmc","attribution":"Abstract of \"Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy\" by Weitong Gao, Yuqin Wang, Yang Zhou et al., https://doi.org/10.1038/s41392-022-01046-3, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.3390/cancers12030738","kind":"review","title":"Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence","authors":["Raju Kumar Vaddepally","Prakash Kharel","Ramesh Kumar Pandey","Rohan Garje","Abhinav Binod Chandra"],"author_count":5,"year":2020,"published":"2020-03-20","venue":"Cancers","cited_by":1198,"doi":"10.3390/cancers12030738","arxiv_id":null,"nct_id":null,"source_url":"http://dx.doi.org/10.3390/cancers12030738","archive_url":"https://space-kitty.com/papers/doi:10.3390/cancers12030738","updated":null,"pmid":"32245016","pmcid":"PMC7140028","openalex_id":"W3010839046","pdf_url":"https://www.mdpi.com/2072-6694/12/3/738/pdf?version=1584707568","abstract":"Cancer is associated with higher morbidity and mortality and is the second leading cause of death in the US. Further, in some nations, cancer has overtaken heart disease as the leading cause of mortality. Identification of molecular mechanisms by which cancerous cells evade T cell-mediated cytotoxic damage has led to the modern era of immunotherapy in cancer treatment. Agents that release these immune brakes have shown activity to recover dysfunctional T cells and regress various cancer. Both cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death-1 (PD-1) play their role as physiologic brakes on unrestrained cytotoxic T effector function. CTLA-4 (CD 152) is a B7/CD28 family; it mediates immunosuppression by indirectly diminishing signaling through the co-stimulatory receptor CD28. Ipilimumab is the first and only FDA-approved CTLA-4 inhibitor; PD-1 is an inhibitory transmembrane protein expressed on T cells, B cells, Natural Killer cells (NKs), and Myeloid-Derived Suppressor Cells (MDSCs). Programmed Death-Ligand 1 (PD-L1) is expressed on the surface of multiple tissue types, including many tumor cells and hematopoietic cells. PD-L2 is more restricted to hematopoietic cells. Blockade of the PD-1 /PDL-1 pathway can enhance anti-tumor T cell reactivity and promotes immune control over the cancerous cells. Since the FDA approval of ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody) in 2011, six more immune checkpoint inhibitors (ICIs) have been approved for cancer therapy. PD-1 inhibitors nivolumab, pembrolizumab, cemiplimab and PD-L1 inhibitors atezolizumab, avelumab, and durvalumab are in the current list of the approved agents in addition to ipilimumab. In this review paper, we discuss the role of each immune checkpoint inhibitor (ICI), the landmark trials which led to their FDA approval, and the strength of the evidence per National Comprehensive Cancer Network (NCCN), which is broadly utilized by medical oncologists and hematologists in their daily practice.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Cancer Immunotherapy and Biomarkers"],"details":null,"provenance":"openalex+europepmc","attribution":"Abstract of \"Review of Indications of FDA-Approved Immune Checkpoint Inhibitors per NCCN Guidelines with the Level of Evidence\" by Raju Kumar Vaddepally, Prakash Kharel, Ramesh Kumar Pandey et al., https://doi.org/10.3390/cancers12030738, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1038/s41573-022-00520-5","kind":"review","title":"Macrophages as tools and targets in cancer therapy","authors":["Alberto Mantovani","Paola Allavena","Federica Marchesi","Cecília Garlanda"],"author_count":4,"year":2022,"published":"2022-08-16","venue":"Nature Reviews Drug Discovery","cited_by":1806,"doi":"10.1038/s41573-022-00520-5","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41573-022-00520-5","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41573-022-00520-5","updated":null,"pmid":"35974096","pmcid":null,"openalex_id":"W4291993576","pdf_url":"https://www.nature.com/articles/s41573-022-00520-5.pdf","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Immune cells in cancer"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1016/j.cell.2018.10.038","kind":"article","title":"Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma","authors":["Moshe Sade-Feldman","Keren Yizhak","Stacey L. Bjorgaard","John P. Ray","Carl G. de Boer","Russell William Jenkins","David Lieb","Jonathan H. Chen","Dennie Tompers Frederick","Michal Barzily-Rokni","Samuel S. Freeman","Alexandre Reuben","Paul Hoover","Alexandra–Chloé Villani","Elena V. Ivanova","Andrew J. Portell","Patrick Hall Lizotte","Amir Reza Aref","Jean-Pierre Eliane","Marc R. Hammond","Hans Vitzthum","Shauna M. Blackmon","Bo Li","Vancheswaran Gopalakrishnan","Sangeetha Meda Reddy"],"author_count":35,"year":2018,"published":"2018-11-01","venue":"Cell","cited_by":2052,"doi":"10.1016/j.cell.2018.10.038","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.cell.2018.10.038","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.cell.2018.10.038","updated":null,"pmid":"30388456","pmcid":null,"openalex_id":"W2899145148","pdf_url":"http://www.cell.com/article/S0092867418313941/pdf","abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Cancer Immunotherapy and Biomarkers"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1073/pnas.1320318110","kind":"article","title":"Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti–PD-L1 immunotherapy in pancreatic cancer","authors":["Christine Feig","James O. Jones","Matthew Kraman","Richard J. B. Wells","Andrew Deonarine","Derek S. Chan","Claire M. Connell","Edward W. Roberts","Qi Zhao","Otávia L. Caballero","Sarah Amalia Teichmann","Tobias Janowitz","Duncan Ian Jodrell","David Arthur Tuveson","Douglas T. Fearon"],"author_count":15,"year":2013,"published":"2013-11-25","venue":"Proceedings of the National Academy of Sciences","cited_by":2098,"doi":"10.1073/pnas.1320318110","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1073/pnas.1320318110","archive_url":"https://space-kitty.com/papers/doi:10.1073/pnas.1320318110","updated":null,"pmid":"24277834","pmcid":null,"openalex_id":"W2086834665","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Cancer Immunotherapy and Biomarkers"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/nrclinonc.2018.29","kind":"review","title":"Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges","authors":["Dai Fukumura","Jonas Kloepper","Zohreh Amoozgar","Dan Gabriel Duda","Rakesh K. Jain"],"author_count":5,"year":2018,"published":"2018-03-06","venue":"Nature Reviews Clinical Oncology","cited_by":2026,"doi":"10.1038/nrclinonc.2018.29","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/nrclinonc.2018.29","archive_url":"https://space-kitty.com/papers/doi:10.1038/nrclinonc.2018.29","updated":null,"pmid":"29508855","pmcid":null,"openalex_id":"W2791328450","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Angiogenesis and VEGF in Cancer"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41571-021-00573-2","kind":"review","title":"Immunotherapies for hepatocellular carcinoma","authors":["Josep Maria Llovet","Florian Castet","Mathias F Heikenwälder","Mala K. Maini","Vincenzo Mazzaferro","David James Pinato","Eli Pikarsky","Andrew Xiuxuan Zhu","Richard S. Finn"],"author_count":9,"year":2021,"published":"2021-11-11","venue":"Nature Reviews Clinical Oncology","cited_by":1840,"doi":"10.1038/s41571-021-00573-2","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41571-021-00573-2","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41571-021-00573-2","updated":null,"pmid":"34764464","pmcid":null,"openalex_id":"W3212903603","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":["Hepatocellular Carcinoma Treatment and Prognosis"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41568-019-0144-6","kind":"review","title":"Tertiary lymphoid structures in the era of cancer immunotherapy","authors":["Catherine Sautès‐Fridman","Florent Petitprez","Julien Caldéraro","Wolf H. Fridman"],"author_count":4,"year":2019,"published":"2019-05-15","venue":"Nature reviews. Cancer","cited_by":1882,"doi":"10.1038/s41568-019-0144-6","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41568-019-0144-6","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41568-019-0144-6","updated":null,"pmid":"31092904","pmcid":null,"openalex_id":"W2945057866","pdf_url":"https://hal.sorbonne-universite.fr/hal-02274060v1/file/s41568-019-0144-6_sans%20marque.pdf","abstract":null,"abstract_license":null,"license":"other-oa","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Cancer Immunotherapy and Biomarkers"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/nri.2017.108","kind":"review","title":"The diverse functions of the PD1 inhibitory pathway","authors":["Arlene H. Sharpe","Kristen E. Pauken"],"author_count":2,"year":2017,"published":"2017-10-09","venue":"Nature reviews. Immunology","cited_by":1982,"doi":"10.1038/nri.2017.108","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/nri.2017.108","archive_url":"https://space-kitty.com/papers/doi:10.1038/nri.2017.108","updated":null,"pmid":"28990585","pmcid":null,"openalex_id":"W2761586559","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":["Cancer Immunotherapy and Biomarkers"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1016/j.cell.2021.01.002","kind":"article","title":"Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition","authors":["Litchfield K","Reading JL","Puttick C","Thakkar K","Abbosh C","Bentham R","Watkins TBK","Rosenthal R","Biswas D","Rowan A","Lim E","Al Bakir M","Turati V","Guerra-Assunção JA","Conde L","Furness AJS","Saini SK","Hadrup SR","Herrero J","Lee SH","Van Loo P","Enver T","Larkin J","Hellmann MD","Turajlic S"],"author_count":28,"year":2021,"published":"2021-01-27","venue":"Cell","cited_by":780,"doi":"10.1016/j.cell.2021.01.002","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.cell.2021.01.002","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.cell.2021.01.002","updated":null,"pmid":"33508232","pmcid":"PMC7933824","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC7933824/pdf","abstract":"Checkpoint inhibitors (CPIs) augment adaptive immunity. Systematic pan-tumor analyses may reveal the relative importance of tumor-cell-intrinsic and microenvironmental features underpinning CPI sensitization. Here, we collated whole-exome and transcriptomic data for >1,000 CPI-treated patients across seven tumor types, utilizing standardized bioinformatics workflows and clinical outcome criteria to validate multivariable predictors of CPI sensitization. Clonal tumor mutation burden (TMB) was the strongest predictor of CPI response, followed by total TMB and CXCL9 expression. Subclonal TMB, somatic copy alteration burden, and histocompatibility leukocyte antigen (HLA) evolutionary divergence failed to attain pan-cancer significance. Dinucleotide variants were identified as a source of immunogenic epitopes associated with radical amino acid substitutions and enhanced peptide hydrophobicity/immunogenicity. Copy-number analysis revealed two additional determinants of CPI outcome supported by prior functional evidence: 9q34 (TRAF2) loss associated with response and CCND1 amplification associated with resistance. Finally, single-cell RNA sequencing (RNA-seq) of clonal neoantigen-reactive CD8 tumor-infiltrating lymphocytes (TILs), combined with bulk RNA-seq analysis of CPI-responding tumors, identified CCR5 and CXCL13 as T-cell-intrinsic markers of CPI sensitivity.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition\" by Litchfield K, Reading JL, Puttick C et al., https://doi.org/10.1016/j.cell.2021.01.002, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."},{"id":"doi:10.1001/jama.2020.17598","kind":"review","title":"Bladder Cancer","authors":["Andrew Thomas Lenis","Patrick M. Lec","Karim Chamie","MSHS MD"],"author_count":4,"year":2020,"published":"2020-11-17","venue":"JAMA","cited_by":1739,"doi":"10.1001/jama.2020.17598","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1001/jama.2020.17598","archive_url":"https://space-kitty.com/papers/doi:10.1001/jama.2020.17598","updated":null,"pmid":"33201207","pmcid":null,"openalex_id":"W3102493364","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":["Bladder and Urothelial Cancer Treatments"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1038/s41571-018-0142-8","kind":"review","title":"Cancer immunoediting and resistance to T cell-based immunotherapy","authors":["Jake S. O’Donnell","Michele W.L. Teng","Mark John Smyth"],"author_count":3,"year":2018,"published":"2018-12-06","venue":"Nature Reviews Clinical Oncology","cited_by":1770,"doi":"10.1038/s41571-018-0142-8","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/s41571-018-0142-8","archive_url":"https://space-kitty.com/papers/doi:10.1038/s41571-018-0142-8","updated":null,"pmid":"30523282","pmcid":null,"openalex_id":"W2902185751","pdf_url":null,"abstract":null,"abstract_license":null,"license":null,"is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":["Cancer Immunotherapy and Biomarkers"],"details":null,"provenance":"openalex","attribution":"Metadata and citation counts: OpenAlex (CC0)."},{"id":"doi:10.1186/s40425-019-0768-9","kind":"article","title":"The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors","authors":["Davis AA","Patel VG"],"author_count":2,"year":2019,"published":"2019-10-26","venue":"Journal for immunotherapy of cancer","cited_by":773,"doi":"10.1186/s40425-019-0768-9","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1186/s40425-019-0768-9","archive_url":"https://space-kitty.com/papers/doi:10.1186/s40425-019-0768-9","updated":null,"pmid":"31655605","pmcid":"PMC6815032","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC6815032/pdf","abstract":"The development of immune checkpoint inhibitors has changed the treatment paradigm for advanced cancers across many tumor types. Despite encouraging and sometimes durable responses in a subset of patients, most patients do not respond. Tumors have adopted the PD-1/PD-L1 axis for immune escape to facilitate tumor growth, which can be leveraged as a potential target for immune checkpoint inhibitors. On this basis, PD-L1 protein expression on tumor or immune cells emerged as the first potential predictive biomarker for sensitivity to immune checkpoint blockade. The goal of our study was to evaluate PD-L1 as a predictive biomarker based on all US Food and Drug Administration (FDA) drug approvals of immune checkpoint inhibitors. We evaluated the primary studies associated with 45 FDA drug approvals from 2011 until April 2019. In total, there were approvals across 15 tumor types. Across all approvals, PD-L1 was predictive in only 28.9% of cases, and was either not predictive (53.3%) or not tested (17.8%) in the remaining cases. There were 9 FDA approvals linked to a specific PD-L1 threshold and companion diagnostic: bladder cancer (N = 3), non-small cell lung cancer (N = 3), triple-negative breast cancer (N = 1), cervical cancer (N = 1), and gastric/gastroesophageal junction cancer (N = 1) with 8 of 9 (88.9%) with immune checkpoint inhibitor monotherapy. The PD-L1 thresholds were variable both within and across tumor types using several different assays, including approvals at the following PD-L1 thresholds: 1, 5, and 50%. PD-L1 expression was also measured in a variable fashion either on tumor cells, tumor-infiltrating immune cells, or both. In conclusion, our findings indicate that PD-L1 expression as a predictive biomarker has limitations and that the decision to pursue testing must be carefully implemented for clinical decision-making.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors\" by Davis AA, Patel VG, https://doi.org/10.1186/s40425-019-0768-9, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified."}],"next":"https://space-kitty.com/api/v1/topics/cancer-immunotherapy/papers?sort=top&limit=25&offset=25"}