TY  - JOUR
A1  - Pelosi, Andrea
A1  - Fiore, Piera Filomena
A1  - Di Matteo, Sabina
A1  - Veneziani, Irene
A1  - Caruana, Ignazio
A1  - Ebert, Stefan
A1  - Munari, Enrico
A1  - Moretta, Lorenzo
A1  - Maggi, Enrico
A1  - Azzarone, Bruno
T1  - Pediatric tumors-mediated inhibitory effect on NK cells: the case of neuroblastoma and Wilms' tumors
JF  - Cancers
N2  - Natural killer (NK) cells play a key role in the control of cancer development, progression and metastatic dissemination. However, tumor cells develop an array of strategies capable of impairing the activation and function of the immune system, including NK cells. In this context, a major event is represented by the establishment of an immunosuppressive tumor microenvironment (TME) composed of stromal cells, myeloid-derived suppressor cells, tumor-associated macrophages, regulatory T cells and cancer cells themselves. The different immunoregulatory cells infiltrating the TME, through the release of several immunosuppressive molecules or by cell-to-cell interactions, cause an impairment of the recruitment of NK cells and other lymphocytes with effector functions. The different mechanisms by which stromal and tumor cells impair NK cell function have been particularly explored in adult solid tumors and, in less depth, investigated and discussed in a pediatric setting. In this review, we will compare pediatric and adult solid malignancies concerning the respective mechanisms of NK cell inhibition, highlighting novel key data in neuroblastoma and Wilms’ tumor, two of the most frequent pediatric extracranial solid tumors. Indeed, both tumors are characterized by the presence of stromal cells acting through the release of immunosuppressive molecules. In addition, specific tumor cell subsets inhibit NK cell cytotoxic function by cell-to-cell contact mechanisms likely controlled by the transcriptional coactivator TAZ. These findings could lead to a more performant diagnostic approach and to the development of novel immunotherapeutic strategies targeting the identified cellular and molecular targets.
KW  - neuroblastoma
KW  - Wilms' tumor
KW  - NK cells
KW  - macrophages
KW  - tumor microenvironment
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239615
SN  - 2072-6694
VL  - 13
IS  - 10
ER  - 
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  -