T memory stem (TSCM) cells are a rare subset of memory lymphocytes endowed with the stem cell–like ability to self-renew and the multipotent capacity to reconstitute the entire spectrum of memory and effector T cell subsets. Cumulative evidence in mice, nonhuman primates and humans indicates that TSCM cells are minimally differentiated cells at the apex of the hierarchical system of memory T lymphocytes. Here we describe emerging findings demonstrating that TSCM cells, owing to their extreme longevity and robust potential for immune reconstitution, are central players in many physiological and pathological human processes. We also discuss how TSCM cell stemness could be leveraged therapeutically to enhance the efficacy of vaccines and adoptive T cell therapies for cancer and infectious diseases or, conversely, how it could be disrupted to treat TSCM cell driven and sustained diseases, such as autoimmunity, adult T cell leukemia and HIV-1.
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This work was supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research (ZIABC011480), the 2014 US National Institutes of Health (NIH) Bench-to-Bedside Award, (to L.G.) NIH grants AI098487, AI106468, AI114235, AI117841, AI120008, AI124776 (to M.L.), the Cancer Research Institute (N.Y.), the Ludwig Cancer Research (N.Y.), the Swiss Cancer League (3507-08-2014), the Swiss National Science Foundation (320030_152856, CRSII3_160708), the SwissTransMed (KIP 18) (to D.E.S.), the Italian Association for Cancer Research and the SUPERSIST (EU-FP7 project) (to C.B.).
The authors declare no competing financial interests.
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Gattinoni, L., Speiser, D., Lichterfeld, M. et al. T memory stem cells in health and disease. Nat Med 23, 18–27 (2017). https://doi.org/10.1038/nm.4241
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Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands
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An unmet need: Harmonization of IL-7 and IL-15 combination for the ex vivo generation of minimally differentiated T cells
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Modeling, optimization, and comparable efficacy of T cell and hematopoietic stem cell gene editing for treating hyper‐IgM syndrome
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