Relationship between Th17 immune response and cancer

Abstract

Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades. Cancer has a close relationship with the immune system and, although Th17 cells are known to play roles in the immune response against microorganisms and in autoimmunity, studies have emphasized their roles in cancer pathogenesis. The Th17 immune response profile is involved in several types of cancer including urogenital, respiratory, gastrointestinal, and skin cancers. This type of immune response exerts pro and antitumor functions through several mechanisms, depending on the context of each tumor, including the protumor angiogenesis and exhaustion of T cells and the antitumor recruitment of T cells and neutrophils to the tumor microenvironment. Among other factors, the paradoxical behavior of Th17 cells in this setting has been attributed to its plasticity potential, which makes possible their conversion into other types of T cells such as Th17/Treg and Th17/Th1 cells. Interleukin (IL)-17 stands out among Th17-related cytokines since it modulates pathways and interacts with other cell profiles in the tumor microenvironment, which allow Th17 cells to prevail in tumors. Moreover, the IL-17 is able to mediate pro and antitumor processes that influence the development and progression of various cancers, being associated with variable clinical outcomes. The understanding of the relationship between the Th17 immune response and cancer as well as the singularities of carcinogenic processes in each type of tumor is crucial for the identification of new therapeutic targets.

Bufei Decoction Improves Lung-Qi Deficiency Syndrome of Chronic Obstructive Pulmonary Disease in Rats by Regulating the Balance of Th17/Treg Cells

“…Meanwhile, they synthesize and release IL-17, a type of inflammatory cytokine, to activate inflammatory cells and induce infiltration of foci, amplifying inflammation [ 22 ]. TGF- β and IL-6 jointly promote transformation of CD4+ T cells towards Th17, which increases the release of IL-17 [ 23 ]. In contrast, Treg cells function to suppress antigen-presenting and effector T cells by directly contacting and/or secreting inhibitory cytokines IL-10 and TGF- β [ 24 ].…”

Th17-Gene Expression Profile in Patients with Chronic Venous Disease and Venous Ulcers: Genetic Modulations and Preliminary Clinical Evidence

“…Several lines of evidence depict a key role of CD4 + Th17+ differentiation in the pathogenesis of different diseases, characterized by a chronic inflammatory stimulation [ 16 ] with complete immune dysregulation, loss of the Treg function, and a high-intensity cytokine stimulation [ 17 ]. The Th17 inflammatory dysregulation, originally described in cell-mediated autoimmune pathogenesis, is nowadays considered a putative mechanism to explain drug resistance in cancer and HIV, as well as in ulcerative colitis and obesity [ 11 , 12 , 14 , 15 , 25 ]. The serum and glucocorticoid regulated kinase 1 (SGK1) is a serine/threonine kinase that displays several homologies with AKT1, originally described as a steroid, insulin, and cAMP-regulated kinase [ 26 ].…”

“…In addition, an increasingly strong role of the Th17 axis in tumor drug resistance and in the progression of HIV infection is emerging [ 12 , 13 ]. Moreover, the Th17 switch plays a key role in several acute and chronic inflammatory diseases, including the COVID-19 cytokine storm [ 11 , 12 , 14 , 15 , 16 ]. A high salt concentration causes a Th17 switch, resulting in increased IL17A production and, consequently, Treg cells’ down-regulation.…”

Emerging role of human microbiome in cancer development and response to therapy: special focus on intestinal microflora

“…Interestingly, the CTX-stimulated pathogenic Th17 response mediated by dysbiotic microbiota is tumor suppressive and prevents the outgrowth of cancer cells. It’s worthwhile to point out that numerous studies documented the contradictory role of Th17 cells in cancer development [ 92 – 94 ]. These cells have a pro-tumorigenic effect by inducing angiogenesis and genetic instability and activating the IL-6-oncogenic STAT-3 signaling pathway.…”