Renal cell tumors convert natural killer cells to a proangiogenic phenotype.

Renal cell tumors convert natural killer cells to a proangiogenic phenotype. Oncotarget. 2020 Jun 30;11(26):2571-2585 Authors: Guan Y, Chambers CB, Tabatabai T, Hatley H, Delfino KR, Robinson K, Alanee SR, Ran S, Torry DS, Wilber A Abstract Natural killer (NK) cells are classically associated with immune surveillance and destruction of tumor cells. Inconsistent with this function, NK cells are found in advanced human tumors including renal cell carcinoma (RCC). NK cells with non-classical phenotypes (CD56+CD16dim/neg; termed decidua NK (dNK) cells) accumulate at the maternal-fetal interface during embryo implantation. These dNK cells are poorly cytotoxic, proangiogenic, and facilitate placenta development. As similarities between embryo implantation and tumor growth exist, we tested the hypothesis that an analogous shift in NK cell phenotype and function occurs in RCC tumors. Our results show that peripheral NK (pNK) cells of RCC patients were uniformly CD56+CD16bright, but lacked full cytotoxic ability. By comparison, RCC tumor-infiltrated NK (TiNK) cells were significantly enriched for CD56+CD16dim-neg cells, a phenotype of dNK cells. Gene expression analysis revealed that angiogenic and inflammatory genes were significantly increased for RCC TiNK versus RCC pNK populations, with enrichment of genes in the hypoxia inducible factor (HIF) 1α pathway. Consistent with this finding, NK cells cultured under hypoxia demonstrated limited ...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research