Mechanisms of antitumor immune response suppression mediated by myeloid-derived suppressor cells in colorectal cancer
TL;DR
Findings reinforce the central role of MDSCs in colorectal cancer progression and highlight their potential as therapeutic targets, but the high heterogeneity of these cells and the lack of standardized methods for their identification remain challenges for their clinical application.
Abstract
Myeloid-derived suppressor cells (MDSCs) play an important role in colorectal cancer progression by contributing to the evasion of the antitumor immune response, treatment resistance, and metastasis formation. This integrative review aimed to analyze the mechanisms by which MDSCs promote the suppression of the antitumor immune response in colorectal cancer, as well as their contribution to disease progression. Studies published between 2020 and 2025 were analyzed using the PubMed and LILACS databases. The selected studies demonstrated that MDSCs employ different mechanisms to promote immunosuppression, including metabolic alterations that limit nutrient availability for immune cells, the production of cytotoxic molecules capable of impairing lymphocyte function, and the secretion of anti-inflammatory mediators that reduce immune system activity. Particularly, the gut microbiota and the presence of Fusobacterium nucleatum stimulate MDSC expansion and activity, contributing to the maintenance of chronic inflammation associated with colorectal cancer. Interactions between these cells and T lymphocytes, invariant natural killer cells, and neutrophils further intensify the immunosuppressive environment, while extracellular vesicles released by tumor and myeloid cells participate in feedback mechanisms that exacerbate immune dysfunction. These findings reinforce the central role of MDSCs in colorectal cancer progression and highlight their potential as therapeutic targets. However, the high heterogeneity of these cells and the lack of standardized methods for their identification remain challenges for their clinical application. Future studies integrating multiparametric flow cytometry, single-cell RNA sequencing, spatial analyses, and metabolomic approaches may provide a broader understanding of MDSC biology and contribute to the development of more specific and effective therapeutic strategies.