Abstract 2889: Novel subset of granulocytic MDSCs as immunosuppressive regulators and therapeutic targets in gastric cancer

Abstract

Abstract The development and progression of cancers are frequently promoted by immunosuppressive cells, such as Treg and myeloid-derived suppressor cells (MDSCs) mediated by various immune checkpoint molecules. Recently, the immune checkpoint inhibitor anti-PD-1 neutralizing antibody has become available for the first-line treatment of gastric cancer (GC) in Japan. However, there is no correlation between PD-1 or PD-L1 expression in Treg or GC tissues and clinical responses to anti-PD-1 antibody. MDSCs are immature myeloid cells thought to suppress immune cell action, but the functional cell surface markers that define MDSCs correlated with cancer progression has not yet been clarified well. In this study, we identified a new subset of potential therapeutic and diagnostic targets for MDSCs in GC patients. Significantly higher levels of immune checkpoint molecules, PD-1 and PD-L1, were expressed on granulocytic MDSCs from advanced than early-stage of GC patients. Interestingly, we found that a subset of G-MDSCs expressed not only PD-1 but also PD-L1 and the pretreatment of G-MDSCs with anti-PD-1 antibody ameliorated T cell responses in vitro. We also found that G-MDSCs isolated from patients treated with anti-PD-1 antibody had a lower ability to suppress T cells. These data indicate that a novel subset of G-MDSCs expressing PD-1 found in advanced GC could be novel therapeutic targets. Citation Format: Takumi Iwasawa, Suguru Yamauchi, Tetsu Fukunaga, Hajime Orita, Kazunori Kato. Novel subset of granulocytic MDSCs as immunosuppressive regulators and therapeutic targets in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2889.