Abstract A37: Blockading PD1 on tumor-primed CD4 T cells instigates antitumor immunity

Abstract

Abstract Despite the remarkable treatment benefits associated with interventional checkpoint PD1 blockade in cancer, most patients ultimately progress on therapy. Revealing mechanisms underlying tumors responsive to PD1 blockade is critical to identifying biomarkers for predicting responses to PD1 therapy and developing novel PD1 combined therapeutic regimens for their broad use in clinic. In a clinically reflective mouse model of spontaneous metastatic breast carcinoma, effective and durable PD1 therapy is dependent on systemic immunity including Type 1 conventional dendritic cells (cDC1: CD8α+DC/CD103+DC), B cells, CD4 T cells, and CD8 T cells. Increased circulating and/or tumor-infiltrating IL12+CD103+DC and IL2+CD4/CD8 T cells are associated with tumors responsive to PD1 therapy. PD1 blockade results in tumor-primed CD44+IL2+CD4 T cells in the periphery regardless of cDC1. Adoptive transfer of PD1 blockade-driven CD44+CD4 T cells ignites protective immunity against new tumors. Neutralization of IL2 post the adoptive transfer abrogates the antitumor immunity. These data suggest the prominent role of PD1 blockade on tumor-primed CD4 T cells in newly induced T cells via cDC1 in response to PD1 therapy. Citation Format: Xingxing Hao, Louis D. Falo III, Guo Chen, Cara D. Carey, Louis D. Falo Jr., Zhaoyang You. Blockading PD1 on tumor-primed CD4 T cells instigates antitumor immunity [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr A37.