TY - JOUR
T1 - Pan-Cancer Immunogenomic Perspective on the Tumor Microenvironment Based on PD-L1 and CD8 T-Cell Infiltration
AU - Ock, Chan Young
AU - Keam, Bhumsuk
AU - Kim, Sehui
AU - Lee, Ju Seog
AU - Kim, Miso
AU - Kim, Tae Min
AU - Jeon, Yoon Kyung
AU - Kim, Dong Wan
AU - Chung, Doo Hyun
AU - Heo, Dae Seog
N1 - Publisher Copyright:
© 2016 American Association for Cancer Research.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Purpose: There is currently no reliable biomarker to predict who would 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 to be 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. Clin Cancer Res; 22(9); 2261-70.
AB - Purpose: There is currently no reliable biomarker to predict who would 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 to be 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. Clin Cancer Res; 22(9); 2261-70.
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U2 - 10.1158/1078-0432.CCR-15-2834
DO - 10.1158/1078-0432.CCR-15-2834
M3 - Article
C2 - 26819449
AN - SCOPUS:84968627725
SN - 1078-0432
VL - 22
SP - 2261
EP - 2270
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 9
ER -