2023
DOI: 10.15252/embj.2022111494
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Antitumor T‐cell function requires CPEB4‐mediated adaptation to chronic endoplasmic reticulum stress

Abstract: Tumor growth is influenced by a complex network of interactions between multiple cell types in the tumor microenvironment (TME). These constrained conditions trigger the endoplasmic reticulum (ER) stress response, which extensively reprograms mRNA translation. When uncontrolled over time, chronic ER stress impairs the antitumor effector function of CD8 T lymphocytes. How cells promote adaptation to chronic stress in the TME without the detrimental effects of the terminal unfolded protein response (UPR) is unkn… Show more

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Cited by 6 publications
(5 citation statements)
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“…We compared immune cell in ltration in patients of two clusters and found an increased in ltration of most immune cells in cluster A patients, suggesting that immune in ltration in tumor tissue of patients was more abundant with higher TUPR-related gene signature and better response potential in immunotherapy of cluster A patients. It is worth noting that the in ltration of CD8 + T cells, which play a tumor-killing role, was signi cantly lower in cluster A than in cluster B patients, and we con rmed a higher T-cell dysfunction score in the cluster B, which may be related to ER stress-dependent T cell differentiation and development [43,44] . However, due to data limitations, our study of ccRCC patients was limited to the bulk RNA-seq analysis of the whole tumor tissue, and further analysis is needed to study the ER stress in speci c non-malignant cells in the TME of patients to explore the effect of TUPR on the function and characteristic remodeling of immune in ltrating cells.…”
Section: Discussionmentioning
confidence: 56%
“…We compared immune cell in ltration in patients of two clusters and found an increased in ltration of most immune cells in cluster A patients, suggesting that immune in ltration in tumor tissue of patients was more abundant with higher TUPR-related gene signature and better response potential in immunotherapy of cluster A patients. It is worth noting that the in ltration of CD8 + T cells, which play a tumor-killing role, was signi cantly lower in cluster A than in cluster B patients, and we con rmed a higher T-cell dysfunction score in the cluster B, which may be related to ER stress-dependent T cell differentiation and development [43,44] . However, due to data limitations, our study of ccRCC patients was limited to the bulk RNA-seq analysis of the whole tumor tissue, and further analysis is needed to study the ER stress in speci c non-malignant cells in the TME of patients to explore the effect of TUPR on the function and characteristic remodeling of immune in ltrating cells.…”
Section: Discussionmentioning
confidence: 56%
“… 31 These proteins are widely expressed in tissues and tumors in partially overlapping patterns. 32 Our study is the first to report and elucidate the function and mechanism of CPEB3 in BCa. The protein has significantly low expression in BCa and is associated with a poor prognosis in patients with the disease.…”
Section: Discussionmentioning
confidence: 82%
“…It is worth noting that the in ltration of CD8+ T cells, which play a tumor-killing role, was signi cantly lower in cluster A than in cluster B patients, and we con rmed a higher T-cell dysfunction score in the cluster B, which may be related to ER stress-dependent T cell differentiation and development. 43,44 However, due to data limitations, our study of ccRCC patients was limited to the bulk RNA-seq analysis of the whole tumor tissue, and further analysis is needed to study the ER stress in speci c non-malignant cells in the TME of patients to explore the effect of TUPR on the function and characteristic remodeling of immune in ltrating cells.…”
Section: Discussionmentioning
confidence: 99%