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

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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.

Graphical Abstract

The illustration depicts the relationship between interleukins and their receptors as a driver of CRC development and the potential therapeutic targets.

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Data Availability

Not Applicable.

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Acknowledgments

The authors of this paper are thankful to Chettinad Academy of Research and Education (CARE) for providing the support infrastructurally and to DST (INSPIRE), Govt of India, and CARE for the financial support.

Funding

This work was partially supported by the DST Inspire research student grant with award number 190963 awarded to Ms. Dikshita Deka and Supervisor Dr. Antara Banerjee and JRF fellowship grant awarded to Ms. Samatha Jain from Chettinad academy of Research and Education.

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Author notes

  1. M. Samatha Jain and Dikshita Deka have contributed equally to this work.

Authors and Affiliations

  1. Faculty of Allied Health Sciences, Chettinad Academy of Research and Education (CARE), Chettinad Hospital and Research Institute (CHRI), Chennai, 603103, India

    Samatha M. Jain, Dikshita Deka, Alakesh Das, Surajit Pathak & Antara Banerjee

  2. Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, Av. Epigmenio Gonzalez, No.500 Fracc. San Pablo, 76130, Querétaro, CP, Mexico

    Sujay Paul

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  1. Samatha M. Jain
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Contributions

The study was designed and conceptualized by AB. The manuscript was written and the artwork was designed by AB, SJ, DD, and AD. The final draft of the manuscript was reviewed and edited by SP, AB, and SP.

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Correspondence to Antara Banerjee.

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Jain, S.M., Deka, D., Das, A. et al. Role of Interleukins in Inflammation-Mediated Tumor Immune Microenvironment Modulation in Colorectal Cancer Pathogenesis. Dig Dis Sci 68, 3220–3236 (2023). https://doi.org/10.1007/s10620-023-07972-8

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