The mitochondrial pyruvate carrier regulates memory T cell differentiation and antitumor function

Wenes, Mathias; Jaccard, Alison; Wyss, Tania; Maldonado‐Pérez, Noelia; Teoh, Shao Thing; Lepez, Anouk; Renaud, Fabrice G.; Franco, Fabien; Waridel, Patrice; Maroun, Céline Yacoub; Tschumi, Benjamin; Dumauthioz, Nina; Zhang, Lianjun; Donda, Alena; Martín, Francisco Javier Escalada San; Migliorini, Denis; Lunt, Sophia Y.; Ho, Ping‐Chih; Romero, Pedro

doi:10.1016/j.cmet.2022.03.013

Cited by 86 publications

(58 citation statements)

References 78 publications

(106 reference statements)

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“…The reasons for the differential prognosis of the three clusters were also revealed in the results of the GSVA analysis. The enrichment pathway in cluster A was associated with anti-tumor ( Kim, 2020 ; Wenes et al, 2022 ). “PARKINSONS DISEASE” and “HUNTINGTONS DISEASE” were significantly enriched in cluster B.…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel cellular senescence-related signature for the prediction of prognosis and immunotherapy response in colon cancer

Dai

Wang²,

Bai³

et al. 2022

Front. Genet.

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The study was conducted to construct a cellular senescence-related risk score signature to predict prognosis and immunotherapy response in colon cancer. Colon cancer data were acquired from the Gene Expression Omnibus and The Cancer Genome Atlas databases. And cellular senescence-related genes were obtained from the CellAge database. The colon cancer data were classified into different clusters based on cellular senescence-related gene expression. Next, prognostic differential genes among clusters were identified with survival analysis. A cellular senescence-related risk score signature was developed by performing the LASSO regression analysis. Finally, PCA analysis, t-SNE analysis, Kaplan-Meier survival analysis, ROC analysis, univariate Cox regression analysis, multivariate Cox regression analysis, C-index analysis, meta-analysis, immune infiltration analysis, and IPS score analysis were used to evaluate the significance of the risk signature for predicting prognosis and immunotherapy response in colon cancer. The colon cancer data were classified into three clusters. The patients in cluster A and cluster B had longer survival. A cellular senescence-related risk score signature was developed. Patients in the low-risk score group showed a better prognosis. The risk score signature could predict colon cancer patients’ prognosis independently of other clinical characteristics. The risk score signature predicted the prognosis of colon cancer patients more accurately than other signatures. Patients in the low-risk score group showed a better response to immunotherapy. The opposite was true for the high-risk score group. In conclusion, the cellular senescence-related risk score signature could be used for the prediction of prognosis and immunotherapy response in colon cancer.

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Section: Discussionmentioning

confidence: 99%

Identification of a novel cellular senescence-related signature for the prediction of prognosis and immunotherapy response in colon cancer

Dai

Wang²,

Bai³

et al. 2022

Front. Genet.

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“…Interestingly, the transfer of MPC KO CD8 + T cells into tumor-bearing mice barely reduced tumor growth as compared with untreated mice, whereas WT CD8 + T cells did, which was related with the downregulated anti-tumor function of CD8 + T cells mediated by the impede of lactate oxidation. Therefore, at least in the tumor-bearing models tested in this study, 1 MPC-mediated mitochondrial pyruvate import is required for sustaining the anti-tumor effector function of TILs.…”

mentioning

confidence: 98%

“…In a recent study published in Cell Metabolism , Wenes et al 1 identified that the inhibition of mitochondrial pyruvate carrier (MPC) led to CD8 + memory T cell (T mem ) differentiation and facilitated superior and long-lasting anti-tumor activity of chimeric antigen receptor (CAR) T cells, which suggests a potential target for enhancing anti-tumor immunity.…”

mentioning

confidence: 99%

“…1 ). 1 MPC deficiency blunted the anti-tumor potential of tumor-infiltrating lymphocytes (TILs) by blocking lactate oxidation in mitochondria. Thus blocking mitochondrial pyruvate uptake promoted memory differentiation of CD8 + T cells.…”

mentioning

confidence: 99%

“…Consistently, MPC inhibitor (MPCi) suppressed glucose incorporation in tricarboxylic acid cycle (TCA) while increased the oxidation of fatty acid and glutamine, resulting in a significant increase in the overall levels of acetyl-CoA in CD8 + T cells. 1 …”

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confidence: 99%

See 2 more Smart Citations

Mitochondrial pyruvate carrier: a metabolic-epigenetic checkpoint orchestrating T cell differentiation

Chen

Wang

2022

Sig Transduct Target Ther

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Glucose metabolism in B cell malignancies: a focus on glycolysis branching pathways

Simon‐Molas,

Del Prete,

Kabanova

2024

Molecular Oncology

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Glucose catabolism, one of the essential pathways sustaining cellular bioenergetics, has been widely studied in the context of tumors. Nevertheless, the function of various branches of glucose metabolism that stem from ‘classical’ glycolysis have only been partially explored. This review focuses on discussing general mechanisms and pathological implications of glycolysis and its branching pathways in the biology of B cell malignancies. We summarize here what is known regarding pentose phosphate, hexosamine, serine biosynthesis, and glycogen synthesis pathways in this group of tumors. Despite most findings have been based on malignant B cells themselves, we also discuss the role of glucose metabolism in the tumor microenvironment, with a focus on T cells. Understanding the contribution of glycolysis branching pathways and how they are hijacked in B cell malignancies will help to dissect the role they have in sustaining the dissemination and proliferation of tumor B cells and regulating immune responses within these tumors. Ultimately, this should lead to deciphering associated vulnerabilities and improve current therapeutic schedules.

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The mitochondrial pyruvate carrier regulates memory T cell differentiation and antitumor function

Cited by 86 publications

References 78 publications

Identification of a novel cellular senescence-related signature for the prediction of prognosis and immunotherapy response in colon cancer

Identification of a novel cellular senescence-related signature for the prediction of prognosis and immunotherapy response in colon cancer

Mitochondrial pyruvate carrier: a metabolic-epigenetic checkpoint orchestrating T cell differentiation

Glucose metabolism in B cell malignancies: a focus on glycolysis branching pathways

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