Transcriptional profiling of paired ccRCC patient CD8+ and CD19+ lymphocytes isolated from tumors, normal tissues, and circulating peripheral blood

Tumor infiltrating lymphocytes are widely associated with positive outcomes, but are still markers of a systemic failed immune response against unresolved cancer. Cancer immunotherapies can reverse their tolerance phenotypes, while preserving tumor-reactivity and neoantigen-specificity shared with circulating immune cells. We performed comprehensive transcriptomic analyses to identify gene signatures common to circulating and tumor infiltrating lymphocytes in the context of clear cell renal cell carcinoma. Modulated genes also associated with disease outcome were validated in other cancer types. Using bioinformatics we identified practical diagnostic markers and actionable targets of the failed immune response. On circulating lymphocytes, three genes could efficiently stratify patients from healthy control donors. From their associations with resistance to cancer immunotherapies as well as viral and bacterial infections, we have uncovered not only pan-cancer, but pan-pathology failed immune response gene signatures. CRCHUM kidney biobank consented, TNM stages I-III clear cell renal cell carcinoma (ccRCC) patients underwent resection at the CHUM, Montreal, Quebec from 2013 to 2017. Microarray analysis was performed on paired patient (pt) CD8+ T cells and CD19+ B cells isolated from ccRCC tumors (TIL, TIL-B), normal tumor-adjacent tissue infiltrating immune cells (TIIC), peripheral blood mononuclear cells (PBMC) from patients (ptPBL), and from age-matched healthy control donors (cdPBL).