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Cell Journal، جلد ۱۶، شماره Suppl ۱، صفحات ۹-۹
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عنوان انگلیسی Is-9: Memory T Cells with Stem-Cell Like Features in Health and Disease
چکیده انگلیسی مقاله The ability to remember and respond more robustly in a second encounter with a pathogen is a critical property of the adaptive immune system and forms the basis of vaccination and adoptive cellular therapy of cancer. This process has been proposed to involve a stem celllike memory T-cell subset, able to rapidly differentiate in effectors and self-renew upon antigen re-encounter. The characterization of such a T-cell subset is not only of basic interest but also of clinical relevance for the development of strategies to target pathogens and cancer by adoptive T-cell therapy. Such a memory T-cell subset, referred to as memory stem T cells (TSCM), has been recently described in humans (Gattinoni et al., Nat. Med. 2011). Our group identified conditions able to instruct naïve T cells into TSCM cells in vitro, thus allowing their expansion and genetic modification in clinically compliant conditions (Cieri et al., Blood 2013). Gene-modified TSCM, defined as postmitotic CD45RA+ CD62L+ CCR7+ IL-7Ra+ CD95+ T lymphocytes, are endowed with exceptional persistence and functional capacity in vitro and in vivo, which could be exploited for cancer adoptive immune-gene therapy. Nevertheless, while self-renewing TSCM would be highly effective in providing long-term immune-surveillance against pathogens and cancer cells, this very same cell subpopulation may also represent a foe when considering T-cell mediated pathologies, such as autoimmune diseases and graft versus host disease (GvHD). In these clinically relevant contexts, TSCM may represent a reservoir of long-lived T cells with undesired and detrimental specificities responsible for therapy resistance and high morbidity. Indeed, we have documented a selective accumulation of TSCM early after allogeneic hematopoietic stem cell transplantation (HSCT), and our data on a small cohort of transplanted patients suggest that the extent of TSCM accumulation one month after HSCT correlates with GvHD occurrence and severity. This presentation will discuss how TSCM cells can be exploited in adoptive immunotherapy, and tamed in the context of T-cell mediated disorders.
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نشانی اینترنتی http://celljournal.org/journal/article/abstract/303
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