DC Field | Value | Language |
---|---|---|
dc.contributor.author | Park, Junsik | ko |
dc.contributor.author | Kim, JC | ko |
dc.contributor.author | Lee, Yong Jae | ko |
dc.contributor.author | Kim, Sunghoon | ko |
dc.contributor.author | Kim, Sang Wun | ko |
dc.contributor.author | Shin, Eui-Cheol | ko |
dc.contributor.author | Lee, Jung Yun | ko |
dc.contributor.author | Park, Su-Hyung | ko |
dc.date.accessioned | 2024-08-23T00:00:05Z | - |
dc.date.available | 2024-08-23T00:00:05Z | - |
dc.date.created | 2024-08-23 | - |
dc.date.created | 2024-08-23 | - |
dc.date.issued | 2024-07 | - |
dc.identifier.citation | JOURNAL FOR IMMUNOTHERAPY OF CANCER, v.12, no.7 | - |
dc.identifier.uri | http://hdl.handle.net/10203/322387 | - |
dc.description.abstract | Background We aimed to investigate the distinct immunological characteristics of the tumor immune microenvironment in epithelial ovarian cancer (EOC) according to BRCA1/2 mutations status and differential PD-1 expression levels. Methods Tumor-infiltrating lymphocytes (TILs) were collected from patients with newly diagnosed advanced-stage EOC (YUHS cohort, n=117). This YUHS cohort was compared with The Cancer Genome Atlas (TCGA) data for ovarian serous cystadenocarcinoma (n=482), in terms of survival outcomes and immune-related gene profiles according to BRCA1/2 status. We used multicolor flow cytometry to characterize the immune phenotypes and heterogeneity of TILs with or without BRCA1/2 mutations. In vitro functional assays were conducted to evaluate the reinvigorating ability of CD8(+ )TILs on anti-PD-1 treatment. Results We found that EOC patients with BRCA1/2 mutations (BRCA1/2mt) exhibited better survival outcomes and significantly higher tumor mutation burden (TMB), compared with BRCA1/2 non-mutated (BRCA1/2wt) patients. Furthermore, CD8(+) TILs within BRCA1/2mt tumors displayed characteristics indicating more severe T-cell exhaustion than their BRCA1/2wt counterparts. Notably, the capacity for anti-PD-1-mediated reinvigoration of CD8(+) TILs was significantly greater in BRCA1/2wt tumors compared with BRCA1/2mt tumors. Additionally, within the BRCA1/2wt group, the frequency of PD-1highCD8(+) TILs was positively correlated with the reinvigoration capacity of CD8(+) TILs after anti-PD-1 treatment. Conclusion Our results highlight unique immune features of CD8(+) TILs in EOC and a differential response to anti-PD-1 treatment, contingent on BRCA1/2 mutation status. These findings suggest that immune checkpoint blockade may be a promising frontline therapeutic option for selected BRCA1/2wt EOC patients. | - |
dc.language | English | - |
dc.publisher | BMJ PUBLISHING GROUP | - |
dc.title | Unique immune characteristics and differential anti-PD-1-mediated reinvigoration potential of CD8+ TILs based on BRCA1/2 mutation status in epithelial ovarian cancers | - |
dc.type | Article | - |
dc.identifier.wosid | 001265089200004 | - |
dc.identifier.scopusid | 2-s2.0-85197813781 | - |
dc.type.rims | ART | - |
dc.citation.volume | 12 | - |
dc.citation.issue | 7 | - |
dc.citation.publicationname | JOURNAL FOR IMMUNOTHERAPY OF CANCER | - |
dc.identifier.doi | 10.1136/jitc-2024-009058 | - |
dc.contributor.localauthor | Shin, Eui-Cheol | - |
dc.contributor.localauthor | Park, Su-Hyung | - |
dc.contributor.nonIdAuthor | Park, Junsik | - |
dc.contributor.nonIdAuthor | Kim, JC | - |
dc.contributor.nonIdAuthor | Lee, Yong Jae | - |
dc.contributor.nonIdAuthor | Kim, Sunghoon | - |
dc.contributor.nonIdAuthor | Kim, Sang Wun | - |
dc.contributor.nonIdAuthor | Lee, Jung Yun | - |
dc.description.isOpenAccess | N | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordAuthor | Tumor infiltrating lymphocyte - TIL | - |
dc.subject.keywordAuthor | Ovarian Cancer | - |
dc.subject.keywordAuthor | Immune Checkpoint Inhibitor | - |
dc.subject.keywordPlus | TUMOR-INFILTRATING LYMPHOCYTES | - |
dc.subject.keywordPlus | ASSOCIATION | - |
dc.subject.keywordPlus | FEATURES | - |
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