TY  - JOUR
A1  - Fiore, Piera Filomena
A1  - Vacca, Paola
A1  - Tumino, Nicola
A1  - Besi, Francesca
A1  - Pelosi, Andrea
A1  - Munari, Enrico
A1  - Marconi, Marcella
A1  - Caruana, Ignazio
A1  - Pistoia, Vito
A1  - Moretta, Lorenzo
A1  - Azzarone, Bruno
T1  - Wilms' tumor primary cells display potent immunoregulatory properties on NK cells and macrophages
JF  - Cancers
N2  - The immune response plays a crucial defensive role in cancer growth and metastasis and is a promising target in different tumors. The role of the immune system in Wilm’s Tumor (WT), a common pediatric renal malignancy, is still to be explored. The characterization of the immune environment in WT could allow the identification of new therapeutic strategies for targeting possible inhibitory mechanisms and/or lowering toxicity of the current treatments. In this study, we stabilized four WT primary cultures expressing either a blastematous (CD56\(^+\)/CD133\(^−\)) or an epithelial (CD56\(^−\)/CD133\(^+\)) phenotype and investigated their interactions with innate immune cells, namely NK cells and monocytes. We show that cytokine-activated NK cells efficiently kill WT cells. However, after co-culture with WT primary cells, NK cells displayed an impaired cytotoxic activity, decreased production of IFNγ and expression of CD107a, DNAM-1 and NKp30. Analysis of the effects of the interaction between WT cells and monocytes revealed their polarization towards alternatively activated macrophages (M2) that, in turn, further impaired NK cell functions. In conclusion, we show that both WT blastematous and epithelial components may contribute directly and indirectly to a tumor immunosuppressive microenvironment that is likely to play a role in tumor progression.
KW  - Wilm's tumor
KW  - NK cells
KW  - macrophages
KW  - tumor microenvironment
KW  - Wilms' tumor
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222981
SN  - 2072-6694
VL  - 13
IS  - 2
ER  -