Abstract Protein synthesis supports robust immune responses. Nutrient competition and global cell stressors in the tumor microenvironment (TME) may impact protein translation in T cells and antitumor immunity. Using human and mouse tumors, we demonstrated here that protein translation in T cells is repressed in solid tumors. Reduced glucose availability to T cells in the TME led to activation of the unfolded protein response (UPR) element eIF2a. Genetic mouse models revealed that translation attenuation mediated by activated p-eIF2a undermines the ability of T cells to suppress tumor growth. Reprogramming T cell metabolism was able to alleviate p-eIF2a accumulation and translational attenuation in the TME, allowing for sustained protein translation. Metabolic and pharmacological approaches showed that proteasome activity mitigates induction of p-eIF2a to support optimal antitumor T cell function, protecting from translation attenuation and enabling prolonged cytokine synthesis in solid tumors. Together, these data identify a new therapeutic avenue to fuel the efficacy of tumor immunotherapy.
Translation Attenuation Protein Translation Tumor Microenvironment Unfolded Protein Response Element Solid Tumors Unfolded Protein Response Nutrient Competition Antitumor Immunity Protein Response Element Mouse Tumors
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Round-ups are the summaries of handpicked papers around trending topics published every week. These would enable you to scan through a collection of papers and decide if the paper is relevant to you before actually investing time into reading it.
Climate change Research Articles published between Nov 21, 2022 to Nov 27, 2022
Nov 28, 2022
Articles Included: 2
No potential conflict of interest was reported by the authors. The conception and design of the study, acquisition of data, analysis and interpretatio...Read More
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