Cytokine- and chemokine-induced inflammatory colorectal tumor microenvironment: Emerging avenue for targeted therapy

Cancer Communications

article

Ajaz A. Bhat¹  Sabah Nisar¹  Mayank Singh³  Bazella Ashraf⁴  Tariq Masoodi¹  Chandra P. Prasad³  Atul Sharma³  Selma Maacha⁵  Thasni Karedath⁶  Sheema Hashem¹  Syed Besina Yasin⁷  Puneet Bagga⁸  Ravinder Reddy⁹  Michael P. Frennaux^1,10  Shahab Uddin^1,11  Punita Dhawan^1,12  Mohammad Haris¹  Muzafar A. Macha^1,14 

[1] Laboratory of Molecular and Metabolic Imaging, Cancer Research Department, Sidra Medicine;These authors contributed equally.;Department of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences ,(AIIMS);Department of Biotechnology, School of Life Sciences, Central University of Kashmir;Division of Translational Medicine, Research Branch, Sidra Medicine;Genomics Core Facility, QBRI, Qatar Foundation;Department of Pathology, Sher-I-Kashmir Institute of Medical Sciences;Department of Diagnostic Imaging, St. Jude Children's Research Hospital;Center for Advanced Metabolic Imaging in Precision Medicine, Department of Radiology, Perelman School of Medicine at the University of Pennsylvania;Academic Health System;Translational Research Institute;Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center;Laboratory Animal Research Center, Qatar University;Watson-Crick Centre for Molecular Medicine, Islamic University of Science and Technology

关键词: chemokine;    colorectal cancer;    cytokine;    drug resistance;    epithelial-mesenchymal transition;    immunosuppression;    immunotherapy;    inflammation;    metastasis;    tumor microenvironment;   

DOI  :  10.1002/cac2.12295

学科分类：社会科学、人文和艺术（综合）

来源: Springer

【 摘 要 】

Colorectal cancer (CRC) is a predominant life-threatening cancer, with liver and peritoneal metastases as the primary causes of death. Intestinal inflammation, a known CRC risk factor, nurtures a local inflammatory environment enriched with tumor cells, endothelial cells, immune cells, cancer-associated fibroblasts, immunosuppressive cells, and secretory growth factors. The complex interactions of aberrantly expressed cytokines, chemokines, growth factors, and matrix-remodeling enzymes promote CRC pathogenesis and evoke systemic responses that affect disease outcomes. Mounting evidence suggests that these cytokines and chemokines play a role in the progression of CRC through immunosuppression and modulation of the tumor microenvironment, which is partly achieved by the recruitment of immunosuppressive cells. These cells impart features such as cancer stem cell-like properties, drug resistance, invasion, and formation of the premetastatic niche in distant organs, promoting metastasis and aggressive CRC growth. A deeper understanding of the cytokine- and chemokine-mediated signaling networks that link tumor progression and metastasis will provide insights into the mechanistic details of disease aggressiveness and facilitate the development of novel therapeutics for CRC. Here, we summarized the current knowledge of cytokine- and chemokine-mediated crosstalk in the inflammatory tumor microenvironment, which drives immunosuppression, resistance to therapeutics, and metastasis during CRC progression. We also outlined the potential of this crosstalk as a novel therapeutic target for CRC. The major cytokine/chemokine pathways involved in cancer immunotherapy are also discussed in this review.

【 授权许可】

CC BY|CC BY-NC-ND