Chromosome 9p copy number gains involving PD-L1 are associated with a specific proliferation and immune-modulating gene expression program active across major cancer types.

摘要: Inhibition of the PD-L1/PD-1 immune checkpoint axis represents one most promising approaches immunotherapy for various cancer types. However, inhibition is successful only in subpopulations patients emphasizing need powerful biomarkers that adequately reflect complex interaction between tumor and system. Recently, recurrent copy number gains (CNG) chromosome 9p involving PD-L1 were detected many types including lung cancer, melanoma, bladder head neck cervical soft tissue sarcoma, prostate gastric ovarian triple-negative breast cancer. Here, we applied functional genomics to analyze global mRNA expression changes associated with gains. Using TCGA data set, identified a list 75 genes strongly up-regulated tumors across As expected, gene set was enriched particular 9p24 (36 23 genes). Furthermore, found enrichment two programs derived from within beyond 9p: implicated cell cycle regulation (22 genes) other modulation system (16 Among these specific cytokines chemokines, e.g. CCL4, CCL8, CXCL10, CXCL11, immunoregulatory such as IFN-G IDO1 well highly expressed proliferation-related kinases PLK1, TTK, MELK CDC20 represent potential drug targets. Collectively, shed light on mechanisms escape stimulation proliferation CNG highlight additional vulnerabilities may be therapeutically exploitable.