Determinants of Colorectal Cancer: An Integrative Immunometabolic Framework Linking Biomarkers, Therapy, and the Diet-Microbiota Axis

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality, with substantial heterogeneity that is not fully explained by genetic alterations alone. Emerging evidence positions metabolic reprogramming as a central driver of tumor behavior, integrating glycolysis, mitochondrial function, lipid and amino acid metabolism, and autophagy into coordinated networks that extend beyond cancer cells to the tumor microenvironment. Tumor-immune metabolic competition and metabolite-mediated signaling shape immune responses, often promoting immunosuppression and resistance to immunotherapy, particularly in microsatellite-stable (MSS) CRC. Systemic factors, including obesity, insulin resistance, and the diet-microbiota axis, further modulate tumor metabolism and immune function, reinforcing disease progression. Metabolic biomarkers reflecting these multi-level interactions, spanning tumor-intrinsic pathways, immune contexture, and host metabolism, offer promising opportunities for improved patient stratification and therapeutic targeting, although clinical validation remains limited. Current treatments, including chemotherapy, targeted agents, and immune checkpoint inhibitors, are effective in selected subgroups but are constrained by resistance mechanisms. In this review, we propose an integrative immunometabolic framework in which tumor, immune, and systemic m

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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