Abstract A138: CD39 increase on cytotoxic T-cell induced by myeloid-derived suppressor cell correlated with poor prognosis in patients with non-small cell lung cancer

Abstract

Background: The factors in tumor microenvironment hinder T-cell activities against tumor cells. The major immunosuppressive cells in tumor sites are myeloid-derived suppressor cell (MDSC), tumor-associated macrophage (TAM), and regulatory T (Treg) cell, and the effector molecules released by those immunosuppressive cells also regulate T-cell activities. Therefore, in this study we examined the pattern of immunosuppressive cells in patients with non-small cell lung cancer. Then, we tested T-cell activities to verify whether the suppressive immune cell populations can influence T-cell activity by monitoring T-cell exhaustion markers. Since CD39 and CD73 expression on cytotoxic T-cell are known to be T-cell exhaustion markers, we analyzed CD39 and CD73 on CD8+ T-cells. Method: Baseline and one week after anti-PD-1 immunotherapy (pembrolizumab and nivolumab) blood samples (n=81) were collected (stage III and IV). For the correlation of suppressive immune cells with disease progression, baseline blood samples from the patients (n=59, stage I~IV) and healthy donors (n=21) were collected. Granulocytic-MDSC, Monocytic-MDSC, TAM, Treg, and CD39+ and CD73+ cytotoxic T-cell population from patients’ PBMC (n=81 and n=59) were analyzed by FACS Verse. For the suppressive assay, isolated T-cells were activated with anti-CD3 and anti-CD28 and then MDSC was co-cultured with T-cells for a week followed by Ki-67, CD39 and CD73 analysis by FACS Verse. Results: G-MDSC (p-value=0.0023), M-MDSC (p-value=0.0032), TAM ((p