Natural killer cells swarm and cross-recruit cytotoxic T cells via CCR5.

Natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) are being trialed as mediators of cellular immunotherapies, but the mechanisms by which these cytotoxic lymphocytes are recruited into solid tumors are incompletely understood. Here, we employ a combination of solid tumor models and quantitative imaging to investigate the interplay between NK cells engaging targets and distal cytotoxic lymphocytes. We find that both murine and human NK cells swarm to tumor targets via secretion of diffusive chemokines that bind the CCR5 receptor. Moreover, we show that activated NK cells and CTLs can directly cross-recruit one another via CCR5. By employing multi-step adoptive transfer protocols in vivo, we demonstrate that tumor-reactive NK cells promote the tumor infiltration of subsequently transferred NK cells and CTLs. Together, these results demonstrate that NK cells can swarm via homotypic chemokine signaling and that NK cells and CTLs engage in direct heterotypic cross-recruitment to targets.