Regulatory T Cells in Colon Cancer: Implications for Pathogenesis, Prognosis and Emerging Therapeutic Strategies

Colon cancer is a highly heterogeneous malignancy with significant global incidence and mortality. The tumor microenvironment (TME) plays a pivotal role in disease progression and treatment response. Among key components of the TME are tumor-infiltrating lymphocytes (TILs), particularly regulatory T cells (Tregs) and effector T cells, whose balance influences cancer outcomes. This review analyzes recent findings regarding the role of Treg cells in colon cancer progression by evaluating preclinical and clinical studies that explore immune cell composition, function, and modulation within the TME. Treg cells demonstrate a dual role in colon cancer. While they suppress effective anti-tumor immune responses, facilitating immune evasion, they may also mitigate chronic inflammation, which contributes to carcinogenesis. High intratumoral Treg levels are correlated with poor prognosis, reduced immunotherapy efficacy, and lower overall survival. Strategies to deplete or reprogram Tregs, such as immune checkpoint inhibition, modulation of T cell plasticity, and selective targeting, have shown promise in enhancing anti-tumor immunity. Complete depletion of Tregs risks inducing autoimmune toxicity. Therefore, a precise understanding of Treg cell subsets and functions is essential. This review highlights the importance of developing targeted immunotherapeutic strategies that modulate Treg activity while preserving immune homeostasis in colon cancer treatment.