DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kim, Byung-Seok | ko |
dc.contributor.author | Kuen, Da-Sol | ko |
dc.contributor.author | Koh, Choong-Hyun | ko |
dc.contributor.author | Kim, Hyung-Don | ko |
dc.contributor.author | Chang, Seon Hee | ko |
dc.contributor.author | Kim, Sehui | ko |
dc.contributor.author | Jeon, Yoon Kyung | ko |
dc.contributor.author | Park, Young-Jun | ko |
dc.contributor.author | Choi, Garam | ko |
dc.contributor.author | Kim, Jiyeon | ko |
dc.contributor.author | Kang, Keon Wook | ko |
dc.contributor.author | Kim, Hye Young | ko |
dc.contributor.author | Kang, Suk-Jo | ko |
dc.contributor.author | Hwang, Shin | ko |
dc.contributor.author | Shin, Eui-Cheol | ko |
dc.contributor.author | Kang, Chang-Yuil | ko |
dc.contributor.author | Dong, Chen | ko |
dc.contributor.author | Chung, Yeonseok | ko |
dc.date.accessioned | 2021-06-21T06:10:15Z | - |
dc.date.available | 2021-06-21T06:10:15Z | - |
dc.date.created | 2021-06-21 | - |
dc.date.created | 2021-06-21 | - |
dc.date.created | 2021-06-21 | - |
dc.date.issued | 2021-06 | - |
dc.identifier.citation | JOURNAL FOR IMMUNOTHERAPY OF CANCER, v.9, no.6 | - |
dc.identifier.issn | 2051-1426 | - |
dc.identifier.uri | http://hdl.handle.net/10203/286010 | - |
dc.description.abstract | Background Multiple types of immune cells producing IL-17 are found in the tumor microenvironment. However, their roles in tumor progression and exhaustion of CD8(+) tumor-infiltrating lymphocytes (TILs) remain unclear. Methods To determine the role of type 17 immunity in tumor, we investigated the growth of B16F10 melanoma and the exhaustion of CD8(+) TILs in Il17a (-/-) mice, Il17a (Cre) R26 (DTA) mice, ROR gamma t inhibitor-treated mice, or their respective control mice. Adoptive transfer of tumor-specific IL-17-producing T cells was performed in B16F10-bearing congenic mice. Anti-CD4 or anti-Ly6G antibodies were used to deplete CD4(+) T cells or CD11b(+)Gr-1(hi) myeloid cells in vivo, respectively. Correlation between type 17 immunity and T cell exhaustion in human cancer was evaluated by interrogating TCGA dataset. Results Depletion of CD4(+) T cells promotes the exhaustion of CD8(+) T cells with a concomitant increase in IL-17-producing CD8(+) T (Tc17) cells in the tumor. Unlike IFN-gamma-producing CD8(+) T (Tc1) cells, tumor-infiltrating Tc17 cells exhibit CD103(+)KLRG1(-)IL-7R alpha(hi) tissue resident memory-like phenotypes and are poorly cytolytic. Adoptive transfer of IL-17-producing tumor-specific T cells increases, while depletion of IL-17-producing cells decreases, the frequency of PD-1(hi)Tim3(+)TOX(+) terminally exhausted CD8(+) T cells in the tumor. Blockade of IL-17 or ROR gamma t pathway inhibits exhaustion of CD8(+) T cells and also delays tumor growth in vivo. Consistent with these results, human TCGA analyses reveal a strong positive correlation between type 17 and CD8(+) T cell exhaustion signature gene sets in multiple cancers. Conclusion IL-17-producing cells promote terminal exhaustion of CD8(+) T cells and tumor progression in vivo, which can be reversed by blockade of IL-17 or ROR gamma t pathway. These findings unveil a novel role for IL-17-producing cells as tumor-promoting cells facilitating CD8(+) T cell exhaustion, and propose type 17 immunity as a promising target for cancer immunotherapy. | - |
dc.language | English | - |
dc.publisher | BMJ PUBLISHING GROUP | - |
dc.title | Type 17 immunity promotes the exhaustion of CD8(+) T cells in cancer | - |
dc.type | Article | - |
dc.identifier.wosid | 000658833100004 | - |
dc.identifier.scopusid | 2-s2.0-85107510342 | - |
dc.type.rims | ART | - |
dc.citation.volume | 9 | - |
dc.citation.issue | 6 | - |
dc.citation.publicationname | JOURNAL FOR IMMUNOTHERAPY OF CANCER | - |
dc.identifier.doi | 10.1136/jitc-2021-002603 | - |
dc.contributor.localauthor | Kang, Suk-Jo | - |
dc.contributor.localauthor | Shin, Eui-Cheol | - |
dc.contributor.nonIdAuthor | Kim, Byung-Seok | - |
dc.contributor.nonIdAuthor | Kuen, Da-Sol | - |
dc.contributor.nonIdAuthor | Koh, Choong-Hyun | - |
dc.contributor.nonIdAuthor | Chang, Seon Hee | - |
dc.contributor.nonIdAuthor | Kim, Sehui | - |
dc.contributor.nonIdAuthor | Jeon, Yoon Kyung | - |
dc.contributor.nonIdAuthor | Park, Young-Jun | - |
dc.contributor.nonIdAuthor | Choi, Garam | - |
dc.contributor.nonIdAuthor | Kim, Jiyeon | - |
dc.contributor.nonIdAuthor | Kang, Keon Wook | - |
dc.contributor.nonIdAuthor | Kim, Hye Young | - |
dc.contributor.nonIdAuthor | Hwang, Shin | - |
dc.contributor.nonIdAuthor | Kang, Chang-Yuil | - |
dc.contributor.nonIdAuthor | Dong, Chen | - |
dc.contributor.nonIdAuthor | Chung, Yeonseok | - |
dc.description.isOpenAccess | Y | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | lymphocytes | - |
dc.subject.keywordAuthor | tumor-infiltrating | - |
dc.subject.keywordAuthor | cytotoxicity | - |
dc.subject.keywordAuthor | immunologic | - |
dc.subject.keywordAuthor | CD8-positive T-lymphocytes | - |
dc.subject.keywordAuthor | cytokines | - |
dc.subject.keywordAuthor | tumor microenvironment | - |
dc.subject.keywordPlus | IL-17 | - |
dc.subject.keywordPlus | TH17 | - |
dc.subject.keywordPlus | AUTOIMMUNITY | - |
dc.subject.keywordPlus | PLASTICITY | - |
dc.subject.keywordPlus | PROGNOSIS | - |
dc.subject.keywordPlus | MELANOMA | - |
dc.subject.keywordPlus | SUBSETS | - |
dc.subject.keywordPlus | PROGRAM | - |
dc.subject.keywordPlus | NETWORK | - |
dc.subject.keywordPlus | HELP | - |
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