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001-es BibID:	BIBFORM076251
035-os BibID:	(cikkazonosító)eaaq1616 (WoS)000430877500003 (Scopus)85046357008
Első szerző:	Chimote, Ameet A.
Cím:	A defect in KCa3.1 channel activity limits the ability of CD8+ T cells from cancer patients to infiltrate an adenosine-rich microenvironment / Ameet A. Chimote, Andras Balajthy, Michael J. Arnold, Hannah S. Newton, Peter Hajdu, Julianne Qualtieri, Trisha Wise-Draper, Laura Conforti
Dátum:	2018
ISSN:	1945-0877 1937-9145
Megjegyzések:	The limited ability of cytotoxic T cells to infiltrate solid tumors hampers immune surveillance and the efficacy of immunotherapies in cancer. Adenosine accumulates in solid tumors and inhibits tumor-specific T cells. Adenosine inhibits T cell motility through the A2A receptor (A2AR) and suppression of KCa3.1 channels. We conducted three-dimensional chemotaxis experiments to elucidate the effect of adenosine on the migration of peripheral blood CD8+ T cells from head and neck squamous cell carcinoma (HNSCC) patients. The chemotaxis of HNSCC CD8+ T cells was reduced in the presence of adenosine, and the effect was greater on HNSCC CD8+ T cells than on healthy donor (HD) CD8+ T cells. This response correlated with the inability of CD8+ T cells to infiltrate tumors. The effect of adenosine was mimicked by an A2AR agonist and prevented by an A2AR antagonist. We found no differences in A2AR expression, 3',5'-cyclic adenosine monophosphate abundance, or protein kinase A type 1 activity between HNSCC and HD CD8+ T cells. We instead detected a decrease in KCa3.1 channel activity, but not expression, in HNSCC CD8+ T cells. Activation of KCa3.1 channels by 1-EBIO restored the ability of HNSCC CD8+ T cells to chemotax in the presence of adenosine. Our data highlight the mechanism underlying the increased sensitivity of HNSCC CD8+ T cells to adenosine and the potential therapeutic benefit of KCa3.1 channel activators, which could increase infiltration of these T cells into tumors.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Science Signaling. - 11 : 527 (2018), p. 1-12. -
További szerzők:	Balajthy András (1988-) (általános orvos) Arnold, Michael J. Newton, Hannah S. Hajdu Péter (1975-) (biofizikus) Qualtieri, Julianne Wise-Draper, Trisha Conforti, Laura
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