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

Oncoimmunology. 2021 Mar 8;10(1):1879530. doi: 10.1080/2162402X.2021.1879530.

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.

Keywords: COX-2; IDO; Natural Killer cells; PGE2; Wilms tumor; immunosuppression; mesenchymal stem cells; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Immunomodulation
  • Killer Cells, Natural*
  • Lymphocyte Activation
  • Receptors, Natural Killer Cell
  • Tumor Microenvironment
  • Wilms Tumor*

Substances

  • Receptors, Natural Killer Cell

Grants and funding

This work was supported by the following grants: Compagnia di San Paolo (ID ROL 20729) (C.C., G.C., G.M.G., G.M.S.); funds from Renal Child Foundation (G.C., G.M.G.); Ministero della Salute (C.C., C.B.); Fondi per la Ricerca di Ateneo 100008-2017-GS-FRA_001, 10008-2018-GS-FRA_001 (C.C., G.M.S.).