| Autor: |
Huff WX; Department of Neurosurgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA. wxia@iupui.edu., Kwon JH; Department of Neurosurgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA. kwonjaeh@iu.edu., Henriquez M; Department of Neurosurgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA. mhenriqu@iu.edu., Fetcko K; Department of Neurology, University of Illinois at Chicago School of Medicine, Chicago, IL 60612, USA. kaleighfetcko@gmail.com., Dey M; Department of Neurosurgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA. mdey@iu.edu. |
| Jazyk: |
angličtina |
| Zdroj: |
International journal of molecular sciences [Int J Mol Sci] 2019 Jun 08; Vol. 20 (11). Date of Electronic Publication: 2019 Jun 08. |
| DOI: |
10.3390/ijms20112810 |
| Abstrakt: |
Functional, tumor-specific CD8 + cytotoxic T lymphocytes drive the adaptive immune response to cancer. Thus, induction of their activity is the ultimate aim of all immunotherapies. Success of anti-tumor immunotherapy is precluded by marked immunosuppression in the tumor microenvironment (TME) leading to CD8 + effector T cell dysfunction. Among the many facets of CD8 + T cell dysfunction that have been recognized-tolerance, anergy, exhaustion, and senescence-CD8 + T cell senescence is incompletely understood. Naïve CD8 + T cells require three essential signals for activation, differentiation, and survival through T-cell receptor, costimulatory receptors, and cytokine receptors. Downregulation of costimulatory molecule CD28 is a hallmark of senescent T cells and increased CD8 + CD28 - senescent populations with heterogeneous roles have been observed in multiple solid and hematogenous tumors. T cell senescence can be induced by several factors including aging, telomere damage, tumor-associated stress, and regulatory T (Treg) cells. Tumor-induced T cell senescence is yet another mechanism that enables tumor cell resistance to immunotherapy. In this paper, we provide a comprehensive overview of CD8 + CD28 - senescent T cell population, their origin, their function in immunology and pathologic conditions, including TME and their implication for immunotherapy. Further characterization and investigation into this subset of CD8 + T cells could improve the efficacy of future anti-tumor immunotherapy. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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