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Blockade of 6-phosphogluconate dehydrogenase generates CD8+ effector T cells with enhanced anti-tumor function

Producción científica: Article › revisión exhaustiva

43 Citas (Scopus)

Resumen

Daneshmandi et al. show that 6-phosphogluconate dehydrogenase (6PGD) in the oxidative pentose phosphate pathway (PPP) is a modulator of CD8+ T cell activation and differentiation. 6PGD blockade reprograms CD8+ T cell metabolism to support superior effector function with higher tumoricidal activity. This metabolic checkpoint represents a key therapeutic target for cancer immunotherapies.

Idioma originalEnglish
Número de artículo108831
PublicaciónCell Reports
Volumen34
N.º10
DOI
EstadoPublished - mar 9 2021

Nota bibliográfica

Publisher Copyright:
© 2021

Financiación

This work was supported by BIDMC seed funds to P.S., 2014-07-1112 target grant from Bayer to P.S., pilot grant 1U24DK097215-01A1 to P.S., and the Markey Cancer Center Redox and Metabolism Shared Resource Facility grant P30CA177558 . P.S. was partially supported by R01CA169470 and W81XWH-15-1-0686 . T.W.-M.F. was supported by 1P01CA163223-01A1 ( NIH ), and V.A.B. was supported by R01CA212605 and R01CA238263 (NIH). We thank Dr. A.N. Lane for valuable and critical reading of the manuscript. We acknowledge technical assistance from BIDMC mitochondria metabolism core and Flow Cytometry core and Harvard Medical School molecular electron microscopy facilities. This work was supported by BIDMC seed funds to P.S. 2014-07-1112 target grant from Bayer to P.S. pilot grant 1U24DK097215-01A1 to P.S. and the Markey Cancer Center Redox and Metabolism Shared Resource Facility grant P30CA177558. P.S. was partially supported by R01CA169470 and W81XWH-15-1-0686. T.W.-M.F. was supported by 1P01CA163223-01A1 (NIH), and V.A.B. was supported by R01CA212605 and R01CA238263 (NIH). We thank Dr. A.N. Lane for valuable and critical reading of the manuscript. We acknowledge technical assistance from BIDMC mitochondria metabolism core and Flow Cytometry core and Harvard Medical School molecular electron microscopy facilities. Experimental design and execution was conducted by S.D. P.S. and T.W.-M.F. Data interpretation was performed by S.D. G.M.W. P.S. T.W.-M.F. and V.A.B. Bioinformatics and data analysis was conducted by S.D. NMR and IC-UHR-Fourier transform mass spectrometry (FTMS) analyses were done by S.D. P.L. R.M.H. and T.C. The manuscript was written and edited by S.D. P.S. T.W.-M.F. V.A.B. P.L. G.M.W. and T.C. V.A.B. has patents on the PD-1 pathway licensed by Bristol-Myers Squibb, Roche, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, and Dako. The authors declare no other competing interests.

FinanciadoresNúmero del financiador
Markey Cancer Center Redox and Metabolism Shared Resource Facility
National Institutes of Health (NIH)R01CA212605
National Childhood Cancer Registry – National Cancer InstituteR01CA238263
Boehringer-Ingelheim
Bristol-Myers Squibb
AstraZeneca
BayerP30CA177558, 1U24DK097215-01A1, 1P01CA163223-01A1, W81XWH-15-1-0686, R01CA169470
Merck
Novartis
Roche Canada
Beth Israel Deaconess Medical Center

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    ASJC Scopus subject areas

    • General Biochemistry, Genetics and Molecular Biology

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