{"id":"doi:10.1186/s13045-018-0582-8","kind":"review","title":"Next generation of immune checkpoint therapy in cancer: new developments and challenges","authors":["Julian Andres Marin-Acevedo","Bhagirathbhai Dholaria","Aixa Elena Soyano","Keith L. Knutson","Saranya Chumsri","Yanyan Lou"],"author_count":6,"year":2018,"published":"2018-03-15","venue":"Journal of Hematology & Oncology","cited_by":806,"doi":"10.1186/s13045-018-0582-8","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1186/s13045-018-0582-8","archive_url":"https://space-kitty.com/papers/doi:10.1186/s13045-018-0582-8","updated":null,"pmid":"29544515","pmcid":null,"openalex_id":"W2799553179","pdf_url":"https://jhoonline.biomedcentral.com/counter/pdf/10.1186/s13045-018-0582-8","abstract":"Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways. Drugs blocking these pathways are currently utilized for a wide variety of malignancies and have demonstrated durable clinical activities in a subset of cancer patients. This approach is rapidly extending beyond CTLA-4 and PD-1/PD-L1. New inhibitory pathways are under investigation, and drugs blocking LAG-3, TIM-3, TIGIT, VISTA, or B7/H3 are being investigated. Furthermore, agonists of stimulatory checkpoint pathways such as OX40, ICOS, GITR, 4-1BB, CD40, or molecules targeting tumor microenvironment components like IDO or TLR are under investigation. In this article, we have provided a comprehensive review of immune checkpoint pathways involved in cancer immunotherapy, and discuss their mechanisms and the therapeutic interventions currently under investigation in phase I/II clinical trials. We also reviewed the limitations, toxicities, and challenges and outline the possible future research directions.","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 \"Next generation of immune checkpoint therapy in cancer: new developments and challenges\" by Julian Andres Marin-Acevedo, Bhagirathbhai Dholaria, Aixa Elena Soyano et al., https://doi.org/10.1186/s13045-018-0582-8, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"cancer-immunotherapy","name":"Cancer Immunotherapy","domain_slug":"medicine"}],"cited_in_dossiers":[]}