Immunological functions of Th17 Cells in colon cancer: From pathogenic mechanisms to emerging treatments

Colon cancer (CC) constitutes a significant global health challenge, characterized by increasing incidence and mortality rates that underscore the necessity for continued investigative efforts. Inflammation-driven cellular and molecular processes are fundamentally implicated in the CC development, progression and pathogenesis. Among these immune effectors, T helper 17 (Th17) cells, a distinct subset of CD4⁺ T lymphocytes, are integral to inflammatory and autoimmune responses and modulate antitumor immunity. In CC, Th17 cells exhibit a dualistic function; they may promote tumorigenesis by sustaining chronic inflammation or exert antitumor effects by enhancing cytotoxic immune response. Notably, critical gaps persist in understanding how Th17 plasticity dynamically governs the balance between immune surveillance and tumor immune evasion, representing a central unresolved controversy in CC progression. Furthermore, while extensive research has shown that Th17 cells interact with the tumor microenvironment (TME) and cancer stem cells (CSCs), the specific mechanisms behind these interactions that facilitate metastasis, invasion, and cellular proliferation are still not fully understood. Several studies have documented an increased proportion of Th17 cells in the peripheral circulation of CC patients. However, conflicting clinical evidence regarding their prognostic significance highlights a major translational challenge for patient stratification and targeted intervention. This review consolidates novel perspectives on the multifaceted contributions of Th17 to CC initiation, progression, and therapy, emphasizing targeted interventions to disrupt inflammatory axes and improve outcomes.