Human renal‐cell carcinoma cells are able to activate natural killer cells

Abstract

We previously reported that natural killer (NK) cells that had infiltrated renal‐cell carcinoma (RCC) proliferated vigorously in culture with interleukin‐2 (IL‐2) and lysed autologous tumor cells. In this study, we investigate the susceptibility of RCC cells to NK‐cell lysis and their ability to stimulate proliferation and increase phenotypic expression and function of NK cells. Cells from primary culture of RCC (p‐RCC cells) were significantly more susceptible to the lysis mediated by human NK3.3 clones than were cells from primary culture of metastatic melanomas. Both RCC‐cell clones and cells from primary culture of non‐tumorous kidneys were also susceptible to lysis by NK3.3 clones and IL‐2‐activated peripheral blood lymphocytes (PBLs). Incubation of NK3.3 clones with p‐RCC cells in the absence of IL‐2 induced proliferation of NK3.3 clones, whereas incubation with cells from primary culture of metastatic melanomas, K562 cells, or any others tested did not. The p‐RCC cells from earlier passages were more potent inducers of NK‐cell proliferation than were those from older passages. Cell‐free culture superna‐tants of p‐RCC cells with or without NK3.3 clones failed to induce NK‐cell proliferation. Incubation of CD16⁺ NK cells purified from PBLs with p‐RCC cells induced higher proliferation of the NK cells only in the presence of IL‐2, whereas incubation with cells from primary culture of metastatic melanomas did not. Incubation of NK3.3 clones with p‐RCC cells resulted in an increase in CD16, CD25 (IL‐2 receptor‐α), and HLA‐DR antigen expression and cytotoxicity in NK3.3 clones. In summary, these results suggest that RCC cells are able to activate NK cells, potentially through cell‐to‐cell interaction.