Abstract
<div>Abstract<p><b>Purpose:</b> 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.</p><p><b>Experimental Design:</b> The RNA expression levels of PD-L1 and CD8A in the samples in the pan-cancer database of TCGA (<i>N</i> = 9,677) were analyzed. Based on their median values, the samples were classified into four tumor microenvironment immune types (TMIT). The mutational profiles, <i>PD-L1</i> amplification, and viral association of the samples were compared according to the four TMITs.</p><p><b>Results:</b> 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 (<i>P</i> < 0.001). <i>PD-L1</i> amplification and oncogenic virus infection were significantly associated with TMIT I, respectively (<i>P</i> < 0.001). A multivariate analysis confirmed that the number of somatic mutations, <i>PD-L1</i> amplification, and Epstein–Barr virus/human papillomavirus infection were independently associated with TMIT I.</p><p><b>Conclusions:</b> TMIT I is associated with a high mutational burden, <i>PD-L1</i> 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. <i>Clin Cancer Res; 22(9); 2261–70. ©2016 AACR</i>.</p><p><i>See related commentary by Schalper et al., p. 2102</i></p></div>
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