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Prognostic perspectives of PD-L1 combined with tumor-infiltrating lymphocytes, Epstein-Barr virus, and microsatellite instability in gastric carcinomas
DC Field | Value | Language |
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dc.contributor.author | Choi, Euno | - |
dc.contributor.author | Chang, Mee Soo | - |
dc.contributor.author | Byeon, Sun-ju | - |
dc.contributor.author | Jin, Heejin | - |
dc.contributor.author | Jung, Kyeong Cheon | - |
dc.contributor.author | Kim, Haeryoung | - |
dc.contributor.author | Lee, Kook Lae | - |
dc.contributor.author | Kim, Won | - |
dc.contributor.author | Park, Jin Hyun | - |
dc.contributor.author | Kim, Ki Hwan | - |
dc.contributor.author | Kim, Jin-Soo | - |
dc.contributor.author | Choi, In Sil | - |
dc.contributor.author | Han, Dong-Seok | - |
dc.contributor.author | Ahn, Hye Seong | - |
dc.contributor.author | Heo, Seung Chul | - |
dc.date.accessioned | 2020-07-15T07:25:24Z | - |
dc.date.available | 2020-07-15T16:26:16Z | - |
dc.date.issued | 2020-06-04 | - |
dc.identifier.citation | Diagnostic Pathology. 2020 Jun 04;15(1):69 | ko_KR |
dc.identifier.issn | 1746-1596 | - |
dc.identifier.uri | https://hdl.handle.net/10371/168595 | - |
dc.description.abstract | Background
The prognostic potential of PD-L1 is currently unclear in gastric carcinomas, although the immune checkpoint PD-1/PD-L1 inhibitors have produced promising results in clinical trials. Methods We explored the prognostic implications of programmed death ligand 1 (PD-L1) in 514 consecutive surgically-resected gastric carcinomas. Overall survival and recurrence-free survival were evaluated. Immunohistochemistry for PD-L1, CD8, FOXP3, and PD-1, and molecular grouping by in situ hybridization for Epstein-Barr virus (EBV)-encoded small RNAs and multiplex PCR for microsatellite instability (MSI) markers were performed. Additionally, to explore the function inherent to PD-L1, PD-L1-specific siRNA transfection, cell proliferation, invasion, migration and apoptosis assays were conducted in five gastric carcinoma cell lines. Results PD-L1(+) tumor and immune cells were observed in 101 (20%) and 244 patients (47%), respectively. Tumoral PD-L1(+)/immune cell PD-L1(-)/CD8+/low tumor-infiltrating lymphocytes (TILs), and more advanced-stage tumors were associated with unfavorable clinical outcomes in the entire cohort through multivariate analysis. Furthermore, tumoral PD-L1(+)/FOXP3+/low TILs were associated with worse clinical outcomes in EBV-positive and MSI-high carcinomas. Tumoral PD-L1(+) alone was an adverse prognostic factor in EBV-positive carcinomas, but not in MSI-high carcinomas, whereas PD-L1(+) immune cells or FOXP3+/high TILs alone were correlated with a favorable prognosis. PD-L1 knockdown in gastric carcinoma cells suppressed cell proliferation, invasion and migration, and increased apoptosis, which were all statistically significant in two EBV(+) cell lines, but not all in three EBV(−) cell lines. Conclusions The prognostic impact of PD-L1 may depend on the tumor microenvironment, and statuses of EBV and MSI, although PD-L1 innately promotes cancer cell survival in cell-based assays. The combination of tumoral PD-L1/immune cell PD-L1/CD8+ TILs may serve as an independent prognostic factor. Tumoral PD-L1(+)/immune cell PD-L1(−)/CD8+/low TILs showing a worse prognosis may be beneficial for combinatorial therapies of anti-PD-L1/PD-1 and anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA4) that would promote effector T cells, thus attack the tumor. | ko_KR |
dc.description.sponsorship | This work was supported by the Basic Science Research Program of the National Research Foundation of Korea, which is funded by the Ministry of Education (2016R1D1A1B01010316). | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | BMC | ko_KR |
dc.title | Prognostic perspectives of PD-L1 combined with tumor-infiltrating lymphocytes, Epstein-Barr virus, and microsatellite instability in gastric carcinomas | ko_KR |
dc.type | Article | ko_KR |
dc.contributor.AlternativeAuthor | 최은오 | - |
dc.contributor.AlternativeAuthor | 장미수 | - |
dc.contributor.AlternativeAuthor | 변선주 | - |
dc.contributor.AlternativeAuthor | 진희진 | - |
dc.contributor.AlternativeAuthor | 정경천 | - |
dc.contributor.AlternativeAuthor | 김해령 | - |
dc.contributor.AlternativeAuthor | 이국래 | - |
dc.contributor.AlternativeAuthor | 김원 | - |
dc.contributor.AlternativeAuthor | 박진현 | - |
dc.contributor.AlternativeAuthor | 김기환 | - |
dc.contributor.AlternativeAuthor | 김진수 | - |
dc.contributor.AlternativeAuthor | 최인실 | - |
dc.contributor.AlternativeAuthor | 한동석 | - |
dc.contributor.AlternativeAuthor | 안혜성 | - |
dc.contributor.AlternativeAuthor | 허승철 | - |
dc.identifier.doi | 10.1186/s13000-020-00979-z | - |
dc.citation.journaltitle | Diagnostic Pathology | ko_KR |
dc.language.rfc3066 | en | - |
dc.rights.holder | The Author(s) | - |
dc.date.updated | 2020-06-16T09:36:38Z | - |
dc.citation.number | 1 | ko_KR |
dc.citation.startpage | 69 | ko_KR |
dc.citation.volume | 15 | ko_KR |
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