A calcium optimum for cytotoxic T lymphocyte and natural killer cell cytotoxicity

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp12820-list-0001">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.