Subpopulations Of Peripheral Blood Lymphocytes And Response To Immunotherapy Across Cancer-Types

Most patients (pts) with advanced cancer do not benefit from immunotherapy (IT) and no predictive and reliable biomarker exists across cancer-types. Here, we studied lymphocyte subpopulations on peripheral blood as easily quantifiable biomarkers of response to IT. From 11/2016 to 06/2019, pts with advanced solid cancer treated with IT at Hospital Clinic Clinical Trials Unit were recruited. Blood samples were collected at baseline (C1D1), at day 1 of cycle 2 (C2D1) and at each radiologic evaluation. Flow cytometry analyses were performed using the lineage and differentiation markers CD25, CD3, FOXP3, CD40L, HLA-DR, CD4, CD62L, CD69, CD8, CTLA4, CD19, CD16/56, CD28, PDL1, PD1, CD45RO/RA and CCR7. Forty-four lymphocyte subpopulations (LSP) were identified and quantified. The primary objective was to associate the levels of LSP with response according to iRECIST criteria. Secondary objectives were progression-free survival (PFS) and overall survival (OS). Cox models, logistic regressions, and areas under the ROC (AUC) were performed. Adjustment for multiple comparisons was considered. 71 evaluable pts with non-small cell lung cancer (25%), colorectal (15%), breast (12%), head and neck (10%), bladder (8%), melanoma (7%), renal (5%), prostate (5%) and others (10%) were recruited. Median age was 62 (22-80), 63% of pts were male and 90% were immune naïve. 50 pts received anti-PD1 (71%) and 69% of ITs were given as monotherapy. The overall response rate (ORR) was 13.5% (95% CI 8-22%). At C1D1, no LSP was found associated with ORR. At C2D1 (n=61) higher levels of effector memory T cells (TEM: CD3+CD45RO+CCR7-) were found associated with response (AUC=0.81, 100% sensitivity, 59.6% specificity, PPV 27.6% and NPV 100%), PFS and OS. The ORR in high-TEM (above median) was 26.7% vs 0% in low-TEM. Compared to low-TEM, high-TEM (above median) was associated with improved PFS (hazard ratio [HR]=0.23; p<0.001) and OS (HR=0.33; p=0.003). All associations were independently of cancer-type, sex, type of immunotherapy and immune-naïve state. Levels of peripheral blood effector memory T-cells during IT might help predict response across cancer-types. Further characterization and validation of this LSP is ongoing.