Wilms' tumor primary cells display potent immunoregulatory properties on NK cells and macrophages
Please always quote using this URN: urn:nbn:de:bvb:20-opus-222981
- 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 blastematousThe 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.…
Author: | Piera Filomena Fiore, Paola Vacca, Nicola Tumino, Francesca Besi, Andrea Pelosi, Enrico Munari, Marcella Marconi, Ignazio Caruana, Vito Pistoia, Lorenzo Moretta, Bruno Azzarone |
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URN: | urn:nbn:de:bvb:20-opus-222981 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Kinderklinik und Poliklinik |
Language: | English |
Parent Title (English): | Cancers |
ISSN: | 2072-6694 |
Year of Completion: | 2021 |
Volume: | 13 |
Issue: | 2 |
Article Number: | 224 |
Source: | Cancers (2021) 13:2, 224. https://doi.org/10.3390/cancers13020224 |
DOI: | https://doi.org/10.3390/cancers13020224 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | Wilms' tumor NK cells; Wilm's tumor; macrophages; tumor microenvironment |
Release Date: | 2022/07/22 |
Date of first Publication: | 2021/01/09 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |