Stromal-like Wilms tumor cells induce human Natural Killer cell degranulation and display immunomodulatory properties towards NK cells

基质样 Wilms 肿瘤细胞诱导人类自然杀伤细胞脱颗粒并表现出针对 NK 细胞的免疫调节特性

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作者:Claudia Cantoni, Martina Serra, Erica Parisi, Bruno Azzarone, Angela Rita Sementa, Luigi Aurelio Nasto, Lorenzo Moretta, Giovanni Candiano, Cristina Bottino, Gian Marco Ghiggeri, Grazia Maria Spaggiari

Abstract

The similarity of stromal-like Wilms tumor (str-WT) cells with mesenchymal stem cells (MSC), suggests their relevant role in the interplay with immune cells in the tumor microenvironment. We investigated the interaction between str-WT cells and NK cells. We observed that str-WT cells expressed some major ligands for activating and inhibitory NK cell receptors. Moreover, they expressed inhibitory checkpoint molecules involved in the negative regulation of anti-tumor immune response. The analysis of the interaction between str-WT cells and NK lymphocytes revealed that activated NK cells could efficiently degranulate upon interaction with str-WT cells. On the other hand, str-WT cells could exert potent inhibitory effects on cytokine-induced activation of NK cell proliferation and phenotype, which were mediated by the production of IDO and PGE2 inhibitory factors. Our data provide insight into the molecular interactions between str-WT cells and NK lymphocytes that may result in different outcomes possibly occurring in the WT microenvironment.

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