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Nat Med. 2017 Jan 6;23(1):18-27. doi: 10.1038/nm.4241.

T memory stem cells in health and disease.

Author information

Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Department of Oncology, Ludwig Cancer Research, Lausanne University Hospital, Lausanne, Switzerland.
Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Experimental Hematology Unit, Division of Immunology Transplantation and Infectious Diseases, Leukemia Unit, San Raffaele Scientific Institute, Milan, Italy.
Hematology Department, Vita Salute San Raffaele University, Milan, Italy.


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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