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  -