Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/15097
Título
Mitochondrial Morphological and Functional Reprogramming Following CD137 (4-1BB) Costimulation.
Autor(es)
Fecha de publicación
2018-07
Cita
Cancer Immunol Res . 2018 Jul;6(7):798-811
Idioma
Inglés
Tipo de documento
journal article
Resumen
T and NK lymphocytes express CD137 (4-1BB), a costimulatory receptor of the TNFR family whose function is exploitable for cancer immunotherapy. Mitochondria regulate the function and survival of T lymphocytes. Herein, we show that CD137 costimulation provided by agonist mAb and CD137L (4-1BBL) induced mitochondria enlargement that resulted in enhanced mitochondrial mass and transmembrane potential in human and mouse CD8+ T cells. Such mitochondrial changes increased T-cell respiratory capacities and were critically dependent on mitochondrial fusion protein OPA-1 expression. Mass and function of mitochondria in tumor-reactive CD8+ T cells from cancer-bearing mice were invigorated by agonist mAb to CD137, whereas mitochondrial baseline mass and function were depressed in CD137-deficient tumor reactive T cells. Tumor rejection induced by the synergistic combination of adoptive T-cell therapy and agonistic anti-CD137 was critically dependent on OPA-1 expression in transferred CD8+ T cells. Moreover, stimulation of CD137 with CD137 mAb in short-term cultures of human tumor-infiltrating lymphocytes led to mitochondria enlargement and increased transmembrane potential. Collectively, these data point to a critical link between mitochondrial morphology and function and enhanced antitumor effector activity upon CD137 costimulation of T cells. Cancer Immunol Res; 6(7); 798-811. ©2018 AACR.
MESH
4-1BB Ligand | Animals | Biomarkers | CD8-Positive T-Lymphocytes | Cytokines | Cytotoxicity, Immunologic | Female | Gene Silencing | Humans | Lymphocytes, Tumor-Infiltrating | Melanoma, Experimental | Membrane Potential, Mitochondrial | Mice | Mice, Knockout | Mitochondria | Neoplasms | RNA, Small Interfering | T-Lymphocytes | Tumor Microenvironment
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- Nombre:
- Mitochondrial Morphological and ...
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- 1.872Mb
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- Artículo