Innate Lymphoid Cells in Colorectal Cancers: A Double-Edged Sword

Abstract

The immune system plays a fundamental role at mucosal barriers in maintaining tissue homeostasis. This is particularly true for the gut where cells are flooded with microbial-derived signals and antigens, which constantly challenge the integrity of the intestinal barrier. Multiple immune cell populations equipped with both pro-and anti-inflammatory functions reside in the gut tissue and these cells tightly regulate intestinal health and functions. Dysregulation of this finely tuned system can progressively lead to autoimmune disease and inflammation-driven carcinogenesis. Over the last decade, the contribution of the adaptive immune system in controlling colorectal cancer has been studied in detail, but the role of the innate system, particularly innate lymphoid cells (ILCs), have been largely overlooked. By sensing their microenvironment, ILCs are essential in supporting gut epithelium repair and controling bacterial-and helminth-mediated intestinal infections, highlighting their important role in maintaining tissue integrity. Accumulating evidence also suggests that they may play an important role in carcinogenesis including intestinal cancers. In this review, we will explore the current knowledge about the pro-and anti-tumor functions of ILCs in colorectal cancer.

Remodelling of colorectal cancer cell signaling by microbiota and immunity in diabetes

“…Innate lymphoid cells (ILCs) found in circulation and enriched at biological frontiers with microorganisms like the intestinal barrier or adipose tissue, represent the first defence against infections (Klose & Artis 2020). ILCs are critical regulators of immune homeostasis, inflammation and cancer detection and their involvement in glucose homeostasis and insulin sensitivity (Huang et al 2019) make them a interesting candidate mediators for the transition from obesity to T2D and CRC. Different ILC1, ILC2 and ILC3 subsets are reminiscent of adaptive T-cell subsets Th1, Th2 and Th17.…”

“…T2D induces loss of receptors NKG2D and NK p46 , related to NK activation and cytotoxicity respectively, leading to NK dysfunction. Interestingly, human CRC samples are also highly infiltrated with NK cells, although circulating NK cells of CRC patients are phenotypically altered and dysfunctional (Huang et al 2019), suggesting that tumour environment might alter NK cell functionality, Fig. 2.…”

Resveratrol Suppresses Cross-Talk between Colorectal Cancer Cells and Stromal Cells in Multicellular Tumor Microenvironment: A Bridge between In Vitro and In Vivo Tumor Microenvironment Study

“…It was described that cancer-associated stromal fibroblasts secrete cancer-stimulating factors such as growth factors and cytokines that transform the extracellular matrix and thus prepare the immediate TME of the tumor cells to facilitate metastasis [ 7 ]. It has been further described that immune cells in the gut play a fundamental role in maintaining tissue homeostasis and that dysregulation within immune cells stimulates chronic inflammation and may promote tumor development [ 9 ], and thus act as important prominent promoters of cancer progression [ 10 ]. In addition, stromal fibroblasts and immune cells in multicellular-TME actively contribute to tumor progression by cancer-induced cross-talk by evading the immunological response through the production of oxygen species and inflammatory cytokines [ 8 , 11 , 12 ].…”

Innate Lymphoid Cells in the Malignant Melanoma Microenvironment

“…This relationship has not been addressed in the context of melanoma progression. However, given the implication of ILCs in fibrogenesis, inflammation, and liver disease, it is tempting to hypothesize that ILC2s play a prometastatic role in the liver in melanoma, as they do in colorectal cancer [155], by secreting factors that promote the development of a desmoplastic stroma [156].…”