Immunotherapy: Open Access
Open Access
ISSN: 2471-9552
ISSN: 2471-9552
Andrew Wilber and Donald S. Torry
Southern Illinois University School of Medicine, USA
Posters & Accepted Abstracts: Immunotherapy (Los Angel)
Statement of the Problem: Natural killer (NK) cells are classically associated with immune surveillance and destruction of tumor cells via cytotoxicity. Inconsistent with this function, influxes of NK cells are found in advanced renal cell carcinoma (RCC) tumors. NK cells with non-classical phenotypes (CD56+CD16dim/neg; termed decidua NK (dNK) cells) accumulate at the maternal-fetal interface during implantation. These dNK cells are poorly cytotoxic, proangiogenic, and facilitate growth of the implant. These effects are mediated, in part, by transforming growth factor beta (TGF�²). The purpose of this study was to determine whether an analogous shift in NK cell phenotype/function occurs in RCC tumors potentiated by tumor-derived TGF�² and hypoxia. Methodology: NK cells from peripheral blood (pNK) and resected tumor tissue (TiNK) of RCC patients were compared to pNK from healthy donors. pNK cells were cultured in the absence or presence of TGF�² and 21% or 1% oxygen to assess conversion by monitoring expression of surface markers and angiogenic genes as well as ability to directly kill target cells. An orthotopic mouse model of RCC was also used, where the murine renal adenocarcinoma cell line, Renca, was implanted directly into the kidneys of Balb/c mice. Findings: TGF�² and hypoxia effectively converted pNK cells to a CD56+CD16dim/ neg phenotype characteristic of dNK cells. These culture-induced dNK-like cells were poorly cytotoxic and produced factors that promote vascularization and tissue remodeling, suggesting a supportive role in tumor progression and metastasis. We also found NK cells isolated from human and murine RCC tumors are phenotypically and functionally different from matched pNK confirming that RCC tumor-related factors are able to alter NK cells. Conclusion & Significance: These studies support a role for TGF�² and hypoxia in conversion of pNK cells to a dNK-like phenotype in RCC tumors. While these characteristics are conceivably beneficial for placentation, they may be exploited to support RCC growth and metastasis.
Email: awilber@siumed.edu