1. 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
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Keunchil Park, Jin Seok Ahn, Jong-Mu Sun, Myung-Ju Ahn, Mi Soon Kim, Hee Jin Cho, Jiae Koh, Kyung Young Lee, and Boram Kim
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0301 basic medicine ,Cancer Research ,Tumor microenvironment ,business.industry ,medicine.medical_treatment ,Immunology ,Immunotherapy ,Peripheral blood mononuclear cell ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Immune system ,030220 oncology & carcinogenesis ,Cancer research ,Myeloid-derived Suppressor Cell ,Cytotoxic T cell ,Medicine ,Nivolumab ,business ,CD8 - 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 Citation Format: Jiae Koh, Kyung Young Lee, Boram Kim, Mi Soon Kim, Hee Jin Cho, Jong-Mu Sun, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn. 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]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A138.
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- 2019
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