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A human memory T-cell subset with stem cell-like properties
A long-lived human memory T cell population that has an enhanced capacity for self-renewal and a multipotent ability to derive central memory, effector memory and effector T cells is described. Expand
Tumor-specific Th17-polarized cells eradicate large established melanoma.
Data indicate that the appropriate in vitro polarization of effector CD4+ T cells is decisive for successful tumor eradication, and this principle should be considered in designing clinical trials involving adoptive transfer-based immunotherapy of human malignancies. Expand
Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8+ T cells.
The findings suggest that the current methodology for selecting T cells for transfer is inadequate and provide new criteria for the generation and the screening of optimal lymphocyte populations for adoptive immunotherapy. Expand
Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells
Findings reveal a key role for Wnt signaling in the maintenance of 'stemness' in mature memory CD8+ T cells and have major implications for the design of new vaccination strategies and adoptive immunotherapies. Expand
Central memory self/tumor-reactive CD8+ T cells confer superior antitumor immunity compared with effector memory T cells.
T tumor-reactive CD8+ T cell populations with the phenotypic and functional attributes of T(CM) may be superior to T(EM)/effector T cells for adoptive immunotherapies using concomitant tumor-antigen vaccination. Expand
Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells
It is found that even in the genetic absence of T reg cells, a nonmyeloablative regimen substantially augmented CD8+ T cell reactivity to self-tissue and tumor, and the restricted availability of homeostatic cytokines can be a contributing factor to peripheral tolerance, as well as a limiting resource for the effectiveness of tumor-specific T cells. Expand
CD8+ T‐cell memory in tumor immunology and immunotherapy
  • Christopher A. Klebanoff, L. Gattinoni, Nicholas P. Restifo
  • Medicine
  • Immunological reviews
  • 1 June 2006
The cellular and molecular mechanisms underlying the formation of distinct central, effector, and exhausted CD8+ T‐cell memory subsets were first described in the setting of acute and chronic viral diseases are now being illuminated as relevant to the tumor‐bearing state. Expand
Th17 cells are long lived and retain a stem cell-like molecular signature.
  • P. Muranski, Zachary A Borman, +19 authors Nicholas P Restifo
  • Biology, Medicine
  • Immunity
  • 23 December 2011
Th17 cells, despite displaying low expression of CD27 and other phenotypic markers of terminal differentiation, efficiently eradicated tumors and caused autoimmunity, were long lived, and maintained a core molecular signature resembling early memory CD8(+) cells with stem cell-like properties. Expand
Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+ T cells via TLR4 signaling.
Disruption of the homeostatic balance between the host and microbes can enhance cell-based tumor immunotherapy, leading to long-term cure of mice with large B16F10 tumors and enhanced autoimmune vitiligo. Expand
IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy.
The efficacy of CD8(+) T cells for adoptive immunotherapy can be influenced by opposing differentiation programs conferred by IL-2 and IL-21, a finding with important implications for the development of cellular cancer therapies. Expand