Human renal-cell carcinoma cells are able to activate natural killer cells.
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 supernatants 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-alpha), 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.
Hayakawa
K
K
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Morita
T
T
Augustus
L B
LB
von Eschenbach
A C
AC
Itoh
K
K
D000943:Antigens, Differentiation / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D011961:Receptors, Fc / Q000378:metabolism; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D006684:HLA-DR Antigens; D011961:Receptors, Fc; D017452:Receptors, IgG; D015375:Receptors, Interleukin-2