Cantoni Claudia, Serra Martina, Parisi Erica, Azzarone Bruno, Sementa Angela Rita, Nasto Luigi Aurelio, Moretta Lorenzo, Candiano Giovanni, Bottino Cristina, Ghiggeri Gian Marco, Spaggiari Grazia Maria
Laboratory of Clinical and Experimental Immunology, Integrated Department of Services and Laboratories, IRCCS Giannina Gaslini Institute, Genoa, Italy.
Department of Experimental Medicine (DIMES) and Center of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy.
Oncoimmunology. 2021 Mar 8;10(1):1879530. doi: 10.1080/2162402X.2021.1879530.
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.
间质性样肾母细胞瘤（str-WT）细胞与间充质干细胞（MSC）的相似性，提示了它们在肿瘤微环境中与免疫细胞相互作用中的相关作用。我们研究了str-WT细胞与自然杀伤细胞（NK细胞）之间的相互作用。我们观察到，str-WT细胞表达了一些用于激活和抑制NK细胞受体的主要配体。此外，它们还表达了参与抗肿瘤免疫反应负调控的抑制性检查点分子。对str-WT细胞与NK淋巴细胞之间相互作用的分析表明，活化的NK细胞在与str-WT细胞相互作用时能够有效地脱颗粒。另一方面，str-WT细胞可对细胞因子诱导的NK细胞增殖和表型激活产生强大的抑制作用，这是由吲哚胺2,3-双加氧酶（IDO）和前列腺素E2（PGE2）抑制因子的产生介导的。我们的数据为str-WT细胞与NK淋巴细胞之间的分子相互作用提供了见解，这些相互作用可能导致在肾母细胞瘤微环境中可能出现的不同结果。
