A calcium optimum for cytotoxic T lymphocyte and natural killer cell cytotoxicity
2018
Key points
Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are required to eliminate cancer cells.
We analysed the Ca2+ dependence of CTL and NK cell cytotoxicity and found that in particular CTLs have a very low optimum of [Ca2+]i (between 122 and 334 nm) and [Ca2+]o (between 23 and 625 μm) for efficient cancer cell elimination, well below blood plasma Ca2+ levels.
As predicted from these results, partial down‐regulation of the Ca2+ channel Orai1 in CTLs paradoxically increases perforin‐dependent cancer cell killing.
Lytic granule release at the immune synapse between CTLs and cancer cells has a Ca2+ optimum compatible with this low Ca2+ optimum for efficient cancer cell killing, whereas the Ca2+ optimum for CTL migration is slightly higher and proliferation increases monotonously with increasing [Ca2+]o.
We propose that a partial inhibition of Ca2+ signals by specific Orai1 blockers at submaximal concentrations could contribute to tumour elimination.
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