Igniting Cold Tumors: Multi-Omics-Driven Strategies to Overcome Immune Evasion and Restore Immune Surveillance

Cold tumors are characterized by insufficient immune cell infiltration and a highly immunosuppressive tumor microenvironment.

• Key mechanisms of immune evasion in cold tumors include activation of the WNT/β-catenin pathway and TGF-β-mediated immunosuppression.
• Metabolic changes, such as lactate accumulation, and abnormal immune checkpoint molecule expression are also associated with immune evasion.
• Proposed therapeutic strategies involve targeting immunosuppressive pathways and reshaping the tumor microenvironment using various approaches.
• Promising interventions include personalized neoantigen vaccines and engineered cell therapies, such as T cell receptor-engineered and natural killer cells.
• Epigenetic regulation mechanisms, like histone deacetylase inhibitors and RNA modifications, may help reverse immune evasion.
• Challenges in clinical translation of these insights include data heterogeneity and limitations of preclinical models.

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