NK cell infiltration is associated with improved overall survival in solid cancers: A systematic review and meta-analysis

The immune landscape of a tumor is highly connected to patient prognosis and response to treatment, but little is known about how natural killer (NK) cells predict overall survival (OS) among patients with solid tumors. We present the first meta-analysis on NK cell infiltration into solid tumors as a prognostic indicator for OS, considering cancer types independently, and together. Samples were collected from 1973 to 2016 with results published between 1989 and 2020. From 53 studies, we found that NK cell infiltration corresponds with decreased risk of death (HR=0.34, 95% CI: 0.26–0.46; p<0.0001). Among studies that investigated the prognostic potential of NK cells in specific regions of the tumor, intraepithelial infiltration was better predictive of OS than NK infiltration in the tumor-adjacent stroma. Generally, NK cell infiltration is lower in advanced-stage and lower-grade tumors; nevertheless, it remains prognostically beneficial. This meta-analysis highlights an important prognostic role of NK cells in solid tumors, but exposes that few studies have considered the contributions of NK cells. Toward NK cell-based immunotherapies, it will be important to understand the conditions under which NK cells can be effective agents of tumor control.