Role of T_H17 cytokines in the control of colorectal cancer

Abstract

Immune/inflammatory cells infiltrate almost all human solid tumors and affect all stages of carcinogenesis as they produce different cytokine subsets. The overproduction of TH17 cytokines marks the early stages of colorectal carcinoma (CRC) and negatively influences the prognosis of CRC patients. Studies with murine models of CRC have delineated the mechanisms by which TH17 cytokines, notably, interleukin (IL)-17A, IL-17F, IL-21, and IL-22, regulate oncogenesis and tumor progression, paving the way to the development of novel anticancer drugs. In this review article, we discuss experimental data supporting the role of TH17 cytokines in the modulation of colorectal tumorigenesis.

The correlations between IL-17 vs. Th17 cells and cancer patient survival: a systematic review

“…Animal models may be helpful to clarify this, as the induction of Th17 cells by IL-6 and TGF-b is clearer in mice than in humans, although the described effects on survival are still contradictory. 12,79 We conclude that while IL-17 primarily promotes tumorigenesis, the subpopulation of IL-17 producing Th17 cells seems to have a tumor-suppressing effect. Future research should use methodology that makes a distinction between soluble IL-17 protein, Th17 cells, and other IL-17 C cells.…”

Batf-dependent Th17 cells critically regulate IL-23 driven colitis-associated colon cancer

“…Elevated interleukin (IL) 23/IL-17a expression levels within solid tumours negatively correlate with disease-free survival and overall survival in patients with CRC and other solid tumour entities 4 5. The cellular origin of the IL-17a production within mucosal tumours is controversially discussed since a number of IL-17a-producing immune cell subsets including CD4 + α/β T cells, so called Th17 cells, γδ T cells, innate lymphoid cells (ILCs) and neutrophils reside in the mucosal compartment 2.…”

Permissive/Protective Interplay of Microbiota with T Cell Adaptive Immune Response in Colon Cancer

“…Enrichment of Th17 cells in the peripheral blood and tumor samples from colon cancer patients has been confirmed in more recent studies (7). In other types of cancer, association of Th17 cells with tumor immunity remains controversial, as both pro-tumor and anti-tumor effects have been reported (59,60,64,65).…”

“…B. fragilis stimulates the production and activation of STAT3, characterized by a selective Th17 response; in fact, blockage of IL-17 prevents colonic hyperplasia and tumor formation in these mice (66). IL-17A signaling can be tumorigenic through several pathways (7,67,68). IL-17A induces mitogen-activated protein kinase (MAPK) and NFκB signaling, the key pathways related to the production of pro-inflammatory cytokines.…”

“…Th17 cells, as an inflammatory subset of CD4+ cells, are the main source of IL-17A, IL-17F, and IL-22 (7). These cells are most frequently found in the gastrointestinal tract, especially in the intestinal lamina propria.…”