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
Authors: Koh Jiae , Lee Kyung Young , Kim Boram , Kim Mi Soon , Cho Hee Jin , Sun Jong-Mu , Ahn Jin Seok , Park Keunchil , Ahn Myung-Ju 
Published: February 2019

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&lt;0.001), and Treg (p&lt;0.001) population were higher in advanced non-small cell lung cancer patients (stage III&IV) compared with stage I and II patients or healthy donors. MDSC isolated from patient’s blood was co-cultured with activated T-cells from the same patient. After one week, T-cell activity was inhibited compared with T-cell alone (p &lt; 0.001, E:T = 5:1, 10:1) confirming suppressive activity of MDSC against T-cells. CD39+CD8+ T-cells were also increased when co-cultured with MDSC. Low MDSC (p-value=0.02) and CD39+CD8+ T-cell population (p-value=0.043) in pre and post-anti-PD-1 immunotherapy and the population decreased group showed better overall survival compared to high and increased MDSC and CD39+CD8+ T-cell population group of the patients. Conclusion: G-MDSC and M-MDSC population increased as disease progressed and MDSC effectively suppressed T-cell activities and induced T-cell exhaustion. TAM and Treg population also increased in advanced non-small cell lung cancer patients. Increased MDSC and CD39+CD8+ T-cells correlated with poor prognosis in patients treated with anti-PD-1 immunotherapy. Therefore, high MDSC and increased CD39 expression on cytotoxic T-cell can be used as a prognostic biomarker for anti-PD-1 immunotherapy in patients with non-small cell lung cancer.

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.