Group 3 innate lymphoid cells: regulating host-commensal bacteria interactions in inflammation and cancer

Abstract

A delicate balance exists between the mammalian immune system and normally beneficial commensal bacteria that colonize the gastrointestinal tract, which is necessary to maintain tissue homeostasis. Dysregulation of these interactions between the host and commensal bacteria is causally associated with chronic inflammation and the development of cancer. In contrast, recent reports have highlighted that commensal bacteria also play an essential role in promoting anti-tumor immune responses in several contexts, highlighting a paradox whereby interactions between the host and commensal bacteria can influence both pro- and anti-tumor immunity. Given the critical roles for group 3 innate lymphoid cells (ILC3s) in regulating inflammation, tissue repair and host-microbe interactions in the intestine, here we discuss new evidence that ILC3s may profoundly influence the development, progression and control of tumors. In this review, we provide an overview of recent advances in understanding the impact of commensal bacteria on tumorigenesis, discuss recent findings identifying ILC3s as critical regulators of host-microbe interactions and highlight the emerging role of this immune cell population in cancer and their potential implication as a therapeutic target.

Keywords: cancer; commensal bacteria; innate lymphoid cells; intestinal homeostasis.

Fig. 1.

The complex interplay between inflammation, cancer and the microbiota. The interactions between inflammation, cancer and the microbiota are reciprocal and complex. Microbiota can promote cancer via multiple mechanisms, for example, by producing genotoxins, by promoting chronic inflammation and cancer-associated inflammation and by eliciting immunosuppression. The tumor can induce a microbial shift that will influence cancer progression. The microbiota can modulate the efficacy of chemotherapy and immunotherapy to potentiate anti-tumor immune responses.

Fig. 2.

The role of ILC3s in the context of cancer. ILC3s can promote tumorigenesis and influence tumor progression. In line with the multiple and context-dependent roles of ILC3s during the inflammatory process, ILC3s may exert pro- or anti-tumor properties in cancer. LTi-like ILC3s can promote formation of ectopic lymphoid-like structures in the tumor microenvironment that can drive a protective adaptive anti-tumor immune response. Delivery of the cytokine IL-12 can potentiate the anti-tumor functions of NCR ⁺ ILC3s by inducing adhesion molecule expression and subsequent leukocyte recruitment to the tumor microenvironment. Stimulation of ILC3s by IL-23 can promote tumorigenesis, implicating the IL-17 pathway. IL-22 production by ILC3s can prevent tumorigenesis during intestinal damage by promoting tissue repair; however, IL-22 also exerts pro-inflammatory and pro-proliferative properties that can promote tumor progression after tumor establishment.