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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,2,24]]},"abstract":"<jats:p>\n                    NADPH is essential for cellular biosynthesis and redox balance in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Here, we demonstrate that the nonoxidative pentose phosphate pathway (non-oxPPP), mediated by transketolase (TKT) and transaldolase (TALDO1), is critical for CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation, proliferation, and memory formation by maintaining NADPH homeostasis. Metabolomic profiling and isotopic tracing revealed upregulated non-oxPPP flux in effector (T\n                    <jats:sub>eff<\/jats:sub>\n                    ) and memory (T\n                    <jats:sub>m<\/jats:sub>\n                    ) CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, enabling a pentose cycle that amplifies NADPH yield and sustains metabolic fitness for T cell immunity. Genetic knockdown or pharmacological inhibition of\n                    <jats:italic toggle=\"yes\">Tkt<\/jats:italic>\n                    or\n                    <jats:italic toggle=\"yes\">Taldo1<\/jats:italic>\n                    impaired NADPH production, leading to ribose-5-phosphate (R5P) accumulation, oxidative stress, reduced lipid synthesis, mitochondrial dysfunction, and compromised T\n                    <jats:sub>eff<\/jats:sub>\n                    cell proliferation, cytokine production, and antitumor efficacy. Conversely, enhancing non-oxPPP activity promoted T\n                    <jats:sub>m<\/jats:sub>\n                    differentiation, persistence, and recall responses. Targeting the non-oxPPP represents a promising strategy to enhance cancer immunotherapy and vaccine efficacy by bolstering T cell effector and memory responses.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2526325123","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T18:44:21Z","timestamp":1771613061000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":5,"title":["Nonoxidative pentose phosphate pathway regulates CD8\n                    <sup>+<\/sup>\n                    T cell immunity by maintaining NADPH homeostasis"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5225-3980","authenticated-orcid":false,"given":"Jingyu","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0869-3951","authenticated-orcid":false,"given":"Qian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]},{"name":"Department of Infectious Diseases, Regulatory Mechanism and Targeted Therapy for Liver Cancer Shiyan Key Laboratory, Hubei Provincial Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Institute of Biomedical Research, Hubei University of Medicine","place":["Shiyan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6868-2023","authenticated-orcid":false,"given":"Zhichao","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1849-9118","authenticated-orcid":false,"given":"Wen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2997-8709","authenticated-orcid":false,"given":"Jingsong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxin","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0401-535X","authenticated-orcid":false,"given":"Zhongji","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Regulatory Mechanism and Targeted Therapy for Liver Cancer Shiyan Key Laboratory, Hubei Provincial Clinical Research Center for Precise Diagnosis and Treatment of Liver Cancer, Taihe Hospital, Institute of Biomedical Research, Hubei University of Medicine","place":["Shiyan, 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