Circulating T Cell Subpopulations Correlate With Immune Responses at the Tumor Site and Clinical Response to PD1 Inhibition in Non-Small Cell Lung Cancer
Circulating T Cell Subpopulations Correlate With Immune Responses at the Tumor Site and Clinical Response to PD1 Inhibition in Non-Small Cell Lung Cancer
Agents targeting the PD1-PDL1 axis have transformed cancer therapy. Factors that influence clinical response to PD1-PDL1 inhibitors include tumor mutational burden, immune infiltration of the tumor, and local PDL1 expression. To identify peripheral correlates of the anti-tumor immune response in the absence of checkpoint blockade, we performed a retrospective study of circulating T cell subpopulations and matched tumor gene expression in melanoma and non-small cell lung cancer (NSCLC) patients. Notably, both melanoma and NSCLC patients whose tumors exhibited increased inflammatory gene transcripts presented high CD4+ and CD8+ central memory T cell (CM) to effector T cell (Eff) ratios in blood. Consequently, we evaluated CM/Eff T cell ratios in a second cohort of NSCLC. The data showed that high CM/Eff T cell ratios correlated with increased tumor PDL1 expression. Furthermore, of the 22 patients within this NSCLC cohort who received nivolumab, those with high CM/Eff T cell ratios, had longer progression-free survival (PFS) (median survival: 91 vs. 215 days). These findings show that by providing a window into the state of the immune system, peripheral T cell subpopulations inform about the state of the anti-tumor immune response and identify potential blood biomarkers of clinical response to checkpoint inhibitors in melanoma and NSCLC.
- University of Florence Italy
- New York University Italy
- Bristol-Myers Squibb (Germany) Germany
- Bristol-Myers Squibb (United States) United States
Male, Lung Neoplasms, Immunology, Programmed Cell Death 1 Receptor, T cells subpopulations, B7-H1 Antigen, Antineoplastic Agents, Immunological, T-Lymphocyte Subsets, Carcinoma, Non-Small-Cell Lung, melanoma, Biomarkers, Tumor, Humans, Melanoma, Aged, RC581-607, Middle Aged, Progression-Free Survival, PD1 and PDL1, lung cancer, Nivolumab, checkpoint blockade, Immunologic diseases. Allergy
Male, Lung Neoplasms, Immunology, Programmed Cell Death 1 Receptor, T cells subpopulations, B7-H1 Antigen, Antineoplastic Agents, Immunological, T-Lymphocyte Subsets, Carcinoma, Non-Small-Cell Lung, melanoma, Biomarkers, Tumor, Humans, Melanoma, Aged, RC581-607, Middle Aged, Progression-Free Survival, PD1 and PDL1, lung cancer, Nivolumab, checkpoint blockade, Immunologic diseases. Allergy
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