T memory stem cells in health and disease: new insights and therapeutic opportunities

Luca Gattinoni, MD
Principal Investigator,
Experimental Transplantation & Immunology Branch,
Center for Cancer Research, National Cancer Institute,
National Institutes of Health

T memory stem cells (TSCM) 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 subsets. Cumulative evidence in mice, non-human primates and humans indicates that TSCM are minimally differentiated cells at the apex of the hierarchical system of memory T lymphocytes. Here we describe emerging findings demonstrating that TSCM, 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 stemness could be therapeutically leveraged to enhance the efficacy of vaccines and adoptive T-cell therapies for cancer and infectious diseases or, conversely, disrupted to treat TSCM-driven and sustained diseases such as autoimmunity, adult T-cell leukemia, and HIV-1.