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World J Gastrointest Oncol. May 15, 2024; 16(5): 1705-1724
Published online May 15, 2024. doi: 10.4251/wjgo.v16.i5.1705
Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression
Damián Sánchez-Ramírez, Mónica G Mendoza-Rodríguez, Omar R Alemán, Fernando A Candanedo-González, Miriam Rodríguez-Sosa, Juan José Montesinos-Montesinos, Mauricio Salcedo, Ismael Brito-Toledo, Felipe Vaca-Paniagua, Luis I Terrazas
Damián Sánchez-Ramírez, Mónica G Mendoza-Rodríguez, Miriam Rodríguez-Sosa, Felipe Vaca-Paniagua, Luis I Terrazas, Unidad de Investigacion en Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, Tlalnepantla 54090, Estado de Mexico, Mexico
Omar R Alemán, Department of Biology, Facultad de Quimica, Universidad Nacional Autonoma de Mexico, Ciudad Universitaria, Mexico City 04510, Mexico
Fernando A Candanedo-González, Department of Pathology, National Medical Center Century XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico
Juan José Montesinos-Montesinos, Laboratorio de Células Troncales Mesenquimales, Unidad de Investigación Médica en Enfermedades Oncológicas, Hospital de Oncología Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico
Mauricio Salcedo, Unidad de Investigacion en Biomedicina y Oncologia Genomica, Instituto Mexciano del Seguro Social, Mexico City 07300, Mexico
Ismael Brito-Toledo, Servicio de Colon y Recto, Hospital de Oncología Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City 06720, Mexico
Felipe Vaca-Paniagua, Luis I Terrazas, Laboratorio Nacional en Salud, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Estado de Mexico, Mexico
Author contributions: Sánchez-Ramírez D, Mendoza-Rodríguez M, and Alemán OR collected and organized the literature, and drafted the manuscript; Candanedo-González FA and Rodríguez-Sosa M developed the graphic art and immunohistochemical slides; Montesinos-Montesinos JJ, Salcedo M, Brito-Toledo I, Vaca-Paniagua F, and Terrazas LI revised the manuscript, corrected, and shortened, also discussed all the sections.
Supported by the Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT) de la Dirección General de Asuntos de Personal Académico, No. IN212722 and No. IA208424; Consejo Mexiquense de Ciencia y Tecnología, No. CS000132; and Consejo Nacional de Humanidades, Ciencia y Tecnología, No. CF-2023-I- 563.
Conflict-of-interest statement: All the authors declare no conflict of interest with this manuscript
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Luis I Terrazas, PhD, Chairman, Senior Scientist, Unidad de Investigacion en Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autonoma de Mexico, 1 Avenida de los Barrios, Tlalnepantla 54090, Estado de Mexico, Mexico. literrazas@unam.mx
Received: January 2, 2024
Revised: February 28, 2024
Accepted: April 1, 2024
Published online: May 15, 2024
Processing time: 128 Days and 9.8 Hours
Abstract

Colorectal cancer (CRC) remains one of the most commonly diagnosed and deadliest types of cancer worldwide. CRC displays a desmoplastic reaction (DR) that has been inversely associated with poor prognosis; less DR is associated with a better prognosis. This reaction generates excessive connective tissue, in which cancer-associated fibroblasts (CAFs) are critical cells that form a part of the tumor microenvironment. CAFs are directly involved in tumorigenesis through different mechanisms. However, their role in immunosuppression in CRC is not well understood, and the precise role of signal transducers and activators of transcription (STATs) in mediating CAF activity in CRC remains unclear. Among the myriad chemical and biological factors that affect CAFs, different cytokines mediate their function by activating STAT signaling pathways. Thus, the harmful effects of CAFs in favoring tumor growth and invasion may be modulated using STAT inhibitors. Here, we analyze the impact of different STATs on CAF activity and their immunoregulatory role.

Keywords: Cancer-associated fibroblasts; Signal transducer and activator of transcription signaling; Colorectal cancer; Immunity; Immunosuppression

Core Tip: The desmoplastic reaction (DR) is characterized by the excessive accumulation of connective tissue that encapsulates the tumor, made up of the recruitment of immune cells, activated fibroblasts, capillary formation, as well as the secretion of extracellular matrix proteins such as collagens, fibronectin, tenascin C, periostin, laminin, growth factors, cytokines, and chemokines. DR has been associated with the poor prognosis of patients and has been reported in various solid tumors: Ductal adenocarcinoma of the pancreas, breast cancer, lung cancer, ovarian cancer, head and neck cancer, colon cancer, and colorectal cancer (CRC), among others. The cells responsible for the generation of DR are cancer-associated fibroblasts, and together, they promote tumor development by increasing the proliferation, invasion, and migration of tumor cells, as well as resistance to chemotherapy and radiotherapy. In fact, the expression of stromal genes associated with DR has been reported to define a poor prognosis in CRC patients.