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- Title
Circulating T Cell Subpopulations Correlate With Immune Responses at the Tumor Site and Clinical Response to PD1 Inhibition in Non-Small Cell Lung Cancer.
- Authors
Manjarrez-Orduño, Nataly; Menard, Laurence C.; Kansal, Selena; Fischer, Paul; Kakrecha, Bijal; Can Jiang; Cunningham, Mark; Greenawalt, Danielle; Patel, Vishal; Minghui Yang; Golhar, Ryan; Carman, Julie A.; Lezhnin, Sergey; Hongyue Dai; Kayne, Paul S.; Suchard, Suzanne J.; Bernstein, Steven H.; Nadler, Steven G.
- Abstract
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.
- Subjects
T cells; IMMUNE response; NON-small-cell lung carcinoma
- Publication
Frontiers in Immunology, 2018, p1
- ISSN
1664-3224
- Publication type
Article
- DOI
10.3389/fimmu.2018.01613