{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T10:46:49Z","timestamp":1787654809421,"version":"build-2736575974"},"reference-count":261,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Ministry of Health &amp; Welfare, Republic of Korea","award":["HI16C2037"],"award-info":[{"award-number":["HI16C2037"]}]},{"name":"a grant of the Korea Health Technology R&amp;D Project through the National Cancer Center, Min-istry of Health and Welfare, Republic of Korea","award":["HA17C0037"],"award-info":[{"award-number":["HA17C0037"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The interaction of immune checkpoint molecules in the tumor microenvironment reduces the anti-tumor immune response by suppressing the recognition of T cells to tumor cells. Immune checkpoint inhibitor (ICI) therapy is emerging as a promising therapeutic option for cancer treatment. However, modulating the immune system with ICIs still faces obstacles with severe immunogenic side effects and a lack of response against many cancer types. Plant-derived natural compounds offer regulation on various signaling cascades and have been applied for the treatment of multiple diseases, including cancer. Accumulated evidence provides the possibility of efficacy of phytochemicals in combinational with other therapeutic agents of ICIs, effectively modulating immune checkpoint-related signaling molecules. Recently, several phytochemicals have been reported to show the modulatory effects of immune checkpoints in various cancers in in vivo or in vitro models. This review summarizes druggable immune checkpoints and their regulatory factors. In addition, phytochemicals that are capable of suppressing PD-1\/PD-L1 binding, the best-studied target of ICI therapy, were comprehensively summarized and classified according to chemical structure subgroups. It may help extend further research on phytochemicals as candidates of combinational adjuvants. Future clinical trials may validate the synergetic effects of preclinically investigated phytochemicals with ICI therapy.<\/jats:p>","DOI":"10.3390\/biom11081107","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T22:35:02Z","timestamp":1627425302000},"page":"1107","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Phytochemicals in Cancer Immune Checkpoint Inhibitor Therapy"],"prefix":"10.3390","volume":"11","author":[{"given":"Juwon","family":"Lee","sequence":"first","affiliation":[{"name":"Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Korea"},{"name":"WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3778-2056","authenticated-orcid":false,"given":"Youngjin","family":"Han","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Korea"},{"name":"SK Biopharmaceuticals Co., Ltd., Seongnam-si 13494, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Korea"},{"name":"Interdisciplinary Program in Cancer Biology, Seoul National University, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HyunA","family":"Jo","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Korea"},{"name":"WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heeyeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Korea"},{"name":"WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soochi","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, School of Medicine, Stanford University, Stanford, CA 94304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Min","family":"Yang","sequence":"additional","affiliation":[{"name":"MedPacto Inc., 92, Myeongdal-ro, Seocho-gu, Seoul 06668, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"MedPacto Inc., 92, Myeongdal-ro, Seocho-gu, Seoul 06668, Korea"},{"name":"Precision Medicine Research Center, Advanced Institute of Convergence Technology, Seoul National University, Suwon 16229, Korea"},{"name":"Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon 16229, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny N.","family":"Dhanasekaran","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"},{"name":"Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7115-4021","authenticated-orcid":false,"given":"Yong Sang","family":"Song","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, College of Medicine, Seoul National University, Seoul 03080, Korea"},{"name":"WCU Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Korea"},{"name":"Interdisciplinary Program in Cancer Biology, Seoul National University, Seoul 03080, Korea"},{"name":"Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul 03080, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Laher, I. 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