Abstract A63: Commensal microbiota promote lung tumorigenesis via γδ T cells

Abstract

Abstract Lung cancer is closely associated with chronic inflammation, but the mechanisms underlying inflammation in this setting have not been clearly defined nor have the specific contributions of particular immune cell types been elucidated. The lung is a mucosal tissue colonized by a diverse bacterial community, and pulmonary infections commonly present in lung cancer patients are linked to clinical outcomes. Here we provide evidence that local microbiota provoke inflammation associated with lung adenocarcinoma by activating lung-resident γδT cells. Germ-free or antibiotic-treated mice were significantly protected from lung tumor initiation and progression induced by Kras mutation and p53 loss. Mechanistically, commensal bacteria stimulated Myd88-dependent IL-1β and IL-23 production from myeloid cells, inducing proliferation and activation of Vγ6+Vδ1+ γδ T cells that produced IL-17 and other effector molecules to promote inflammation and tumor cell proliferation. Our findings clearly link local microbiota-immune crosstalk to lung tumorigenesis, and thereby define key cellular and molecular mediators that may serve as effective targets in lung cancer treatment and prevention. Citation Format: Chengcheng Jin, Chen Zhao, Georgia Lagoudas, Arjun Bhutkar, Bo Hu, Tyler Jacks. Commensal microbiota promote lung tumorigenesis via γδ T cells [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr A63.