TH9, TH17, and TH22 Cell Subsets and Their Main Cytokine Products in the Pathogenesis of Colorectal Cancer

Abstract

In recent years, several newly identified T helper (TH) cell subsets, such as TH9, TH17, and TH22 cells, and their respective cytokine products, IL-9, IL-17, and IL-22, have been reported to play critical roles in the development of chronic inflammation in the colorectum. Since chronic inflammation is a potent driving force for the development of human colorectal cancer (CRC), the contributions of TH9/IL-9, TH17/IL-17, and TH22/IL-22 in the pathogenesis of CRC have recently become an increasingly popular area of scientific investigation. Extensive laboratory and clinical evidence suggests a positive relationship between these new TH subsets and the growth and formation of CRC, whereas, administration of IL-9, IL-17, and IL-22 signaling inhibitors can significantly alter the formation of colorectal chronic inflammation or CRC lesions in animal models, suggesting that blocking these cytokine signals might represent promising immunotherapeutic strategies. This review summarizes recent findings and currently available data for understanding the vital role and therapeutic significance of TH9/IL-9, TH17/IL-17, and TH22/IL-22 in the development of colorectal tumorigenesis.

Age Distribution of Multiple Functionally Relevant Subsets of CD4+ T Cells in Human Blood Using a Standardized and Validated 14-Color EuroFlow Immune Monitoring Tube

“…Moreover, similar transcriptomics/phenotypic associations were also confirmed for other minor Th-cell subsets, such as Th1/Th17 and Th22 cells: mixed expression of Th1-and Th17-related genes by Th1/Th17 cells and overexpression of the AHR transcription factor as well as IL26 in Th22 cells (1,5,55,56). Of note, Th22 cells also showed overexpression of the IL13 gene, IL13 being a key effector cytokine in immune responses against intracellular parasites and in the modulation of tumor cell growth and apoptosis (57,58).…”

Differential gene expression of tumor-infiltrating CD4 + T cells in advanced versus early stage colorectal cancer and identification of a gene signature of poor prognosis

“…In the CRC microenvironment, naïve CD4 + T cells can differentiate to all Th phenotypes (Th1/Th2/Th17/Th22/Treg) depending on the expression of transcription factors and cytokine release. 25,55 Additionally, in CRC patients the higher expression of Th17 transcripts are associated with poor prognosis, whereas higher expression of Th1 and cytotoxicity transcripts are associated with favorable prognosis. 25 However, Th2 transcripts have no prognostic importance in CRC.…”

IL-10 and IL-22 in Mucosal Immunity: Driving Protection and Pathology

“…Although Th17 cells can produce both IL-22 and IL-17, it is noteworthy that a distinct human CD4 + T cell subset, known as Th22 cells, only produces IL-22 but not IL-17 ( 17 , 38 ). Th22 cells produce their own cytokine profiles, such as IL-22, IL-26, and IL-33, which can be stimulated by IL-6, IL-21, and IL-23 ( 39 ); however, there is a debate about whether the Th22 cells are derived from Th17 cells. Apart from the adaptive cells, innate cells, including the ILCs and lymphoid tissue inducer (LTi) cells also serve as important sources of IL-22, particularly in the gastrointestinal tract ( 40 ).…”