Role of Interleukins in Inflammation-Mediated Tumor Immune Microenvironment Modulation in Colorectal Cancer Pathogenesis

Abstract

Introduction: Tumor cells invade and spread through a procedure termed as epithelial-to-mesenchymal cell transition (EMT). EMT is triggered by any alterations in the genes that encode the extracellular matrix (ECM) proteins, the enzymes that break down the ECM, and the activation of the genes that causes the epithelial cell to change into a mesenchymal type. The transcription factors NF-κB, Smads, STAT3, Snail, Zeb, and Twist are activated by inflammatory cytokines, for instance, Tumor Necrosis Factor, Tumor Growth Factors, Interleukin-1, Interleukin-8, and Interleukin-6, which promotes EMT.

Materials: The current piece of work has been reviewed from the literature works published in last 10 years on the role interleukins in inflammation-mediated tumor immune microenvironment modulation in colorectal cancer pathogenesis utilizing the databases like Google Scholar, PubMed, Science Direct.

Results: Recent studies have demonstrated that pathological situations, such as epithelial malignancies, exhibit EMT characteristics, such as the downregulation of epithelial markers and the overexpression of mesenchymal markers. Several growing evidence have also proved its existence in the human colon during the carcinogenesis of colorectal cancer. Most often, persistent inflammation is thought to be one factor contributing to the initiation of human cancers, such as colorectal cancer (CRC). Therefore, according to epidemiologic and clinical research, people with ulcerative colitis and Crohn's disease have a greater probability of developing CRC.

Conclusion: A substantial amount of data points to the involvement of the NF-κB system, SMAD/STAT3 signaling cascade, microRNAs, and the Ras-mitogen-activated protein kinase/Snail/Slug in the epithelial-to-mesenchymal transition-mediated development of colorectal malignancies. As a result, EMT is reported to play an active task in the pathogenesis of colorectal cancer, and therapeutic interventions targeting the inflammation-mediated EMT might serve as a novel strategy for treating CRC. The illustration depicts the relationship between interleukins and their receptors as a driver of CRC development and the potential therapeutic targets.

Keywords: Colorectal cancer; Drug resistance; Epithelial–Mesenchymal Transition; Inflammation; Interleukins; Therapeutics; Tumor microenvironment.