Abstract PR-004: Radiation modulates hepatic siphoning of T cells to improve immunotherapy efficacy

Abstract

Abstract It is not well established which site(s) in a metastatic patients should be targeted with radiotherapy to elicit responses to immunotherapy. While cancer frequently metastasizes to the liver, it is unknown if liver immune tolerance mechanisms contribute to cancer outcomes. We have found that that liver metastases diminish immunotherapy efficacy systemically in patients and preclinical models. We and others have shown that patients with liver metastases derive limited benefit from immune checkpoint inhibitors. In preclinical models, we show that liver metastases siphon activated CD8+ T cells from systemic circulation and induce their apoptosis within the liver. Consequently, liver metastases create a systemic immune desert. Similarly, patients with liver metastases have reduced adaptive immune responses. In preclinical models, liver-directed radiotherapy eliminates hepatic siphoning of T cells. Thus, liver metastases cause acquired immunotherapy resistance through CD8+ T cell deletion, and the combination of liver-directed radiotherapy and immunotherapy could promote systemic anti-tumor immunity. Citation Format: Michael Green, Jiali Yu, Shasha Li, Theodore S. Lawrence, Weiping Zou. Radiation modulates hepatic siphoning of T cells to improve immunotherapy efficacy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PR-004.