Chronic inflammation is recognized as a causative factor in the development of cancer and recent paradigms suggest that microbe-driven chronic inflammation is causally associated with the development and progression of cancer in the colon. Further, recent studies in mice have implicated innate lymphoid cells (ILC) as a key cell population that regulates intestinal inflammation. Group 3 innate lymphoid cells (ILC3) are essential regulators of immunity, inflammation and tissue homeostasis in the intestine, yet their role in cancer remains poorly defined. Here, we identify that ILC3 are associated with both human and mouse colon tumors. Tumor-associated ILC3 are selectively localized within lymphoid aggregates and exhibit a unique phenotypic profile as compared with nonmalignant tissue. Critically, mice with a selective deletion of ILC3-specific MHCII exhibit a striking increased susceptibility to intestinal tissue damage and develop highly invasive and flat colorectal tumors. These data demonstrate a protective role for antigen-presenting ILC3 in the context of cancer development and progression in the intestine, and suggest that further interrogation may lead to the development of novel immunotherapeutic strategies in colon cancer.
Citation Format: Jeremy Goc, Nick Bessman, Sheena Sahota, Flamar Anne Laure, Gregory Putzel, David Withers, Janelle Arthur, Manish Shah, Gregory Sonnenberg. A protective role for group 3 innate lymphoid cells in colitis-associated colorectal cancer [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A075.