Inflammatory Response and Immunomodulation in Colorectal Cancer: Interaction between Intestinal Barriers, Cytokines, and Tissue Damage in Tumor Progression

Abstract

Colorectal cancer (CRC) is a multifactorial disease in which chronic inflammation, intestinal dysbiosis, and immune dysregulation converge to simultaneously promote tumor progression and immune evasion. These alterations activate inflammatory signaling pathways and generate a tumor microenvironment that is both pro-inflammatory and immunosuppressive, fostering angiogenesis, epithelial–mesenchymal transition (EMT), and resistance to apoptosis. The aim of this study was to analyze the relationship between inflammatory mediators, immune cells, and CRC progression during the 2020–2025 period, identifying potential immunomodulatory therapeutic targets. A systematic and descriptive review was conducted using PubMed, Scopus, and Web of Science, including in vitro, in vivo, and clinical studies focused on cytokines and the tumor microenvironment. The findings showed that sustained activation of the JAK/STAT3, NF-κB, and SMAD pathways, together with disruption of the intestinal barrier, contributes to maintaining a chronically inflammatory microenvironment. Cytokines such as IL-6, TNF-α, IL-10, and TGF-β exhibit a dual role, initially exerting protective functions but later promoting tumor development. Additionally, M2 macrophage polarization, neutrophil accumulation, and the expansion of regulatory T cells were associated with immunosuppression and metastatic potential.