{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:01:47Z","timestamp":1789153307909,"version":"build-2803163510"},"reference-count":157,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017M3A9E9072669 2017M3A9E8029717 NRF-2019M3A9B6065231 2019M3A9B6065221 2018R1A2A1A05076997 2017R1A5A1014560"],"award-info":[{"award-number":["2017M3A9E9072669 2017M3A9E8029717 NRF-2019M3A9B6065231 2019M3A9B6065221 2018R1A2A1A05076997 2017R1A5A1014560"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    The success of immune checkpoint inhibitors (ICIs), notably anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) as well as inhibitors of CTLA-4, programmed death 1 (PD-1), and programmed death ligand-1 (PD-L1), has revolutionized treatment options for solid tumors. However, the lack of response to treatment, in terms of\n                    <jats:italic>de novo<\/jats:italic>\n                    or acquired resistance, and immune related adverse events (IRAE) remain as hurdles. One mechanisms to overcome the limitations of ICIs is to target other immune checkpoints associated with tumor microenvironment. Immune checkpoints such as lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), V-domain immunoglobulin suppressor of T cell activation (VISTA), B7 homolog 3 protein (B7-H3), inducible T cell costimulatory (ICOS), and B and T lymphocyte attenuator (BTLA) are feasible and promising options for treating solid tumors, and clinical trials are currently under active investigation. This review aims to summarize the clinical aspects of the immune checkpoints and introduce novel agents targeting these checkpoints.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2021.681320","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T02:17:33Z","timestamp":1620267453000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":106,"title":["Clinical Insights Into Novel Immune Checkpoint Inhibitors"],"prefix":"10.3389","volume":"12","author":[{"given":"Jii Bum","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Jun","family":"Ha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Ryun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/j.immuni.2016.05.001","article-title":"Lag-3, Tim-3, and TIGIT: Co-inhibitory Receptors with Specialized Functions in Immune Regulation","volume":"44","author":"Anderson","year":"2016","journal-title":"Immunity"},{"key":"B2","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.coi.2011.12.005","article-title":"Tim-3, a Negative Regulator of Anti-tumor Immunity","volume":"24","author":"Anderson","year":"2012","journal-title":"Curr. 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