Abstract PO-057: Host cell-derived TXA2-mediated Gq signaling in tumor cells promotes tumor immune evasion

Abstract

Abstract Tumor-derived prostaglandin E2 (PGE2) promotes tumor progression through evasion of anti-tumor immunity. However, little is known about how PGE2 secretion is regulated within tumor tissues. Here, we show that host cell-derived thromboxane A2 (TXA2) triggers tumor cells to secrete PGE2, resulting in the evasion of anti-tumor immunity. An induction of Ca2+ transients in BrafV600E mouse melanoma cells is sufficient to trigger PGE2 secretion. The frequency of Ca2+ transients is markedly higher in melanoma cells implanted into mice than those in vitro. We show that t he melanoma cells deficient in TXA2 receptor or Gq subunit α do not exhibit Ca2+ transients in vivo nor evade anti-tumor immunity, as do not melanoma cells deficient in cyclooxygenases (COX). Motesanib, a VEGF receptor antagonist, suppresses Ca2+ transients, suggesting the involvement of tumor endothelial cells in the TXA2 production within tumor tissue. These resultsresults identifyresults identifyidentify TXA2 as a critical promotertargetof PGE2-dependent tumorigenesis. Citation Format: Kenta Terai, Yoshinobu Konishi, Hiroshi Ichise, Tetsuya Watabe, Yukari Sando, Takefumi Kondo, Choji Oki, Shinya Tsukiji, Yoko Hamazaki, Yasuhiro Murakawa, Akifumi Takaori-Kondo, Michiyuki Matsuda. Host cell-derived TXA2-mediated Gq signaling in tumor cells promotes tumor immune evasion [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-057.