CSDE1 in tumour immunology: spatiotemporal translational reprogramming and immune microenvironment remodeling

The tumour immune microenvironment (TIME) can be considered a dynamic ecosystem, which requires rapid proteomic adaptation for immune evasion. While transcriptional control is undoubtedly significant, post-transcriptional mechanisms, most notably translational regulation, facilitate immediate proteome rewiring. Cold Shock Domain Containing E1 (CSDE1), an RNA-binding protein, has emerged as a pivotal upstream regulator of translational control, orchestrating multiple facets of mRNA metabolism, including translation initiation, elongation, and stability. While its context-dependent roles in tumourigenesis are recognised, the function of CSDE1 in immune regulation remains incompletely understood.

This review synthesises emerging evidence to position CSDE1 as a central architect of immunosuppression through spatiotemporal translational reprogramming. The present study delineates the manner in which CSDE1 facilitates tumour-intrinsic immune evasion by suppressing antigen presentation and neutralising immunogenic signalling (e.g. cGAS-STING), while concurrently dictating the fates of immune cells - ranging from the development of haematopoietic stem cells to the differentiation of T and B cells. These findings are integrated to propose a novel conceptual framework of spatiotemporal translational reprogramming. This framework posits that CSDE1 decodes the cellular context to dynamically configure translational output across temporal (tumour initiation, progression, therapy resistance) and spatial (cytoplasm, nucleoplasmic reticulum, stress granules, immunological synapse) dimensions. Finally, we explore the therapeutic targeting of CSDE1 through combinatory genotoxic therapy, neoantigen vaccines, immunotherapy sensitisation, and physical stimulation, proposing CSDE1 as a novel therapeutic nexus to overcome resistance in tumour immunotherapy.

CSDE1 has been identified as a central context-decoder and a promising therapeutic nexus in the TIME. However, its duality and essential physiological roles pose significant translational challenges.