Translational Recoding in Tumors: Dual Role in Adaptation and Immune Evasion, Emerging as Therapeutic Target

Protein synthesis is normally tightly regulated, but in cancer, ribosomes often deviate from canonical translation. This "translational recoding" generates altered protein products, expanding proteome diversity. These deviations arise from cell-intrinsic changes and extrinsic pressures within the tumor microenvironment, enhancing stress adaptation, metabolic, and phenotypic plasticity. Understanding this process is crucial as it simultaneously promotes tumor fitness and generates tumor-specific antigens, offering a unique therapeutic vulnerability.

This review synthesizes current research on translational recoding in cancer. It examines the drivers and consequences of these ribosomal deviations, which lead to altered protein products and expanded proteome diversity within tumor cells. The authors analyze the dual role of recoding in promoting tumor adaptation and shaping immune surveillance, ultimately exploring its potential as a targetable vulnerability for novel cancer therapies.

The review highlights that in cancer, ribosomes frequently deviate from canonical protein synthesis, a process termed translational recoding. This phenomenon significantly expands the proteome diversity within tumor cells by generating altered protein products. These recoding events are driven by both cell-intrinsic alterations and extrinsic pressures within the tumor microenvironment.

Translational recoding plays a dual role: it promotes tumor fitness by enhancing stress adaptation, metabolic flexibility, and phenotypic plasticity, while simultaneously generating novel peptides that function as tumor-specific antigens. These tumor-specific antigens are crucial as they can elicit robust immune responses against the cancer. Consequently, the authors identify emerging therapeutic strategies focused on modulating translational fidelity and inducing specific recoding events. These approaches aim to enhance tumor immunogenicity and improve the efficacy of existing immunotherapy responses by making tumors more visible to the immune system.