Intravital Imaging Reveals Distinct Dynamics for Natural Killer and CD8+ T Cells during Tumor Regression

SummaryRecognition of NKG2D ligands by natural killer (NK) cells plays an important role during antitumoral responses. To address how NKG2D engagement affects intratumoral NK cell dynamics, we performed intravital microscopy in a Rae-1β-expressing solid tumor. This NKG2D ligand drove NK cell accumulation, activation, and motility within the tumor. NK cells established mainly dynamic contacts with their targets during tumor regression. In sharp contrast, cytotoxic T lymphocytes (CTLs) formed stable contacts in tumors expressing their cognate antigen. Similar behaviors were observed during effector functions in lymph nodes. In vitro, contacts between NK cells and their targets were cytotoxic but did not elicit sustained calcium influx nor adhesion, whereas CTL contact stability was critically dependent on extracellular calcium entry. Altogether, our results offer mechanistic insight into how NK cells and CTLs can exert cytotoxic activity with remarkably different contact dynamics.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (156 K)Download as PowerPoint slideHighlights► NKG2D ligand expression in solid tumors drives NK cell accumulation and motility ► CTLs and NK cells form stable and transient contacts with tumor cells, respectively ► Distinct calcium influx patterns underlie differences in contact dynamics