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Pan-cancer immunogenomic perspective on the tumor microenvironment based on PD-L1 and CD8 T-cell infiltration

Cited 130 time in Web of Science Cited 127 time in Scopus
Authors
Ock, Chan-Young; Keam, Bhumsuk; Kim, Sehui; Lee, Ju-Seog; Kim, Miso; Kim, Tae Min; Jeon, Yoon Kyung; Kim, Dong-Wan; Chung, Doo Hyun; Heo, Dae Seog
Issue Date
2016-05
Citation
Clinical Cancer Research, Vol.22 No.9, pp.2261-2270
Abstract
Purpose: There is currently no reliable biomarker to predict who wou ld benefit from anti-PD-1/PD-L1 inhibitors. We comprehensively analyzed the immunogenomic properties in The Cancer Genome Atlas (TCGA) according to the classification of tumor into four groups based on PD-L1 status and tumor-infiltrating lymphocyte recruitment (TIL), a combination that has been suggested tobe a theoretically reliable biomarker of anti-PD-1/PD-L1 inhibitors. Experimental Design: The RNA expression levels of PD-L1 and CD8A in the samples in the pan-cancer database of TCGA (N = 9,677) were analyzed. Based on their median values, the samples were classified into four tumor microenvironment immune types (TMIT). The mutational profiles, PD-L1 amplification, and viral association of the samples were compared according to the four TMITs. Results: The proportions of TMIT I, defined by high PD-L1 and CD8A expression, were high in lung adenocarcinoma (67.1%) and kidney clear cell carcinoma (64.8%) among solid cancers. The number of somatic mutations and the proportion of microsatellite instable-high tumor in TMIT I were significantly higher than those in other TMITs, respectively (P < 0.001). PD-L1 amplification and oncogenic virus infection were significantly associated with TMIT I, respectively (P < 0.001). A multivariate analysis confirmed that the number of somatic mutations, PD-L1 amplification, and Epstein-Barr virus/human papillomavirus infection were independently associated with TMIT I. Conclusions: TMIT I is associated with a high mutational burden, PD-L1 amplification, and oncogenic viral infection. This integrative analysis highlights the importance of the assessment of both PD-L1 expression and TIL recruitment to predict responders to immune checkpoint inhibitors. (C) 2016 AACR.
ISSN
1078-0432
URI
https://hdl.handle.net/10371/165316
DOI
https://doi.org/10.1158/1078-0432.CCR-15-2834
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College of Medicine/School of Medicine (의과대학/대학원)Cancer Research Institute (암연구소)Journal Papers (저널논문_암연구소)
College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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