Natural Killer Cells and Neuroblastoma: tumor recognition, escape mechanisms and possible novel immunotherapeutic approaches
Neuroblastoma (NB) is the most common extra-cranial solid tumor of childhood and arises from developing sympathetic nervous system. Most primary tumors localize in the abdomen, the adrenal gland or lumbar sympathetic ganglia. Amplification in tumor cells of MYCN, the major oncogenic driver, patients...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00056/full |
| _version_ | 1818132352754253824 |
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| author | Cristina eBottino Cristina eBottino Alessandra eDondero Francesca eBellora Lorenzo eMoretta Franco eLocatelli Franco eLocatelli Vito ePistoia Alessandro eMoretta Alessandro eMoretta Roberta eCastriconi Roberta eCastriconi |
| author_facet | Cristina eBottino Cristina eBottino Alessandra eDondero Francesca eBellora Lorenzo eMoretta Franco eLocatelli Franco eLocatelli Vito ePistoia Alessandro eMoretta Alessandro eMoretta Roberta eCastriconi Roberta eCastriconi |
| author_sort | Cristina eBottino |
| collection | DOAJ |
| description | Neuroblastoma (NB) is the most common extra-cranial solid tumor of childhood and arises from developing sympathetic nervous system. Most primary tumors localize in the abdomen, the adrenal gland or lumbar sympathetic ganglia. Amplification in tumor cells of MYCN, the major oncogenic driver, patients’ age over 18 months and the presence at diagnosis of a metastatic disease (stage IV, M) identify NB at high risk of treatment failure. Conventional therapies did not significantly improve the overall survival of these patients. Moreover, the limited landscape of somatic mutations detected in NB is hampering the development of novel pharmacological approaches. Major efforts aim to identify novel NB-associated surface molecules that activate immune responses and/or direct drugs to tumor cells and tumor-associated vessels. PVR (Poliovirus Receptor) and B7-H3 are promising targets, since they are expressed by most high-risk NB, are upregulated in tumor vasculature and are essential for tumor survival/invasiveness. PVR is a ligand of DNAM-1 activating receptor that triggers the cytolytic activity of Natural Killer (NK) cells against NB. In animal models targeting of PVR with an attenuated oncolytic poliovirus induced tumor regression and elimination. Also B7-H3 was successfully targeted in preclinical studies and is now being tested in phase I/II clinical trials. B7-H3 down-regulates NK cytotoxicity, providing NB with a mechanism of escape from immune response. The immunosuppressive potential of NB can be enhanced by the release of soluble factors that impair NK cell function and/or recruitment. Among these, TGF-β1 modulates the cytotoxicity receptors and the chemokine receptor repertoire of NK cells.<br/>Here, we summarize the current knowledge on the main cell surface molecules and soluble mediators that modulate the function of NK cells in NB, considering the pros and cons that must be taken into account in the design of novel NK cell-based immunotherapeutic approaches. <br/> |
| first_indexed | 2024-12-11T08:35:28Z |
| format | Article |
| id | doaj.art-a08c490ebd2d40dc81d3a6770c0ff710 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T08:35:28Z |
| publishDate | 2014-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-a08c490ebd2d40dc81d3a6770c0ff7102022-12-22T01:14:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242014-02-01510.3389/fimmu.2014.0005679437Natural Killer Cells and Neuroblastoma: tumor recognition, escape mechanisms and possible novel immunotherapeutic approachesCristina eBottino0Cristina eBottino1Alessandra eDondero2Francesca eBellora3Lorenzo eMoretta4Franco eLocatelli5Franco eLocatelli6Vito ePistoia7Alessandro eMoretta8Alessandro eMoretta9Roberta eCastriconi10Roberta eCastriconi11School of Medicine, University of GenovaIstituto Giannina GasliniSchool of Medicine, University of GenovaSchool of Medicine, University of GenovaIstituto Giannina GasliniSchool of Medicine, University of PaviaOspedale Bambino GesùIstituto Giannina GasliniSchool of Medicine, University of GenovaUniversity of GenovaSchool of Medicine, University of GenovaUniversity of GenovaNeuroblastoma (NB) is the most common extra-cranial solid tumor of childhood and arises from developing sympathetic nervous system. Most primary tumors localize in the abdomen, the adrenal gland or lumbar sympathetic ganglia. Amplification in tumor cells of MYCN, the major oncogenic driver, patients’ age over 18 months and the presence at diagnosis of a metastatic disease (stage IV, M) identify NB at high risk of treatment failure. Conventional therapies did not significantly improve the overall survival of these patients. Moreover, the limited landscape of somatic mutations detected in NB is hampering the development of novel pharmacological approaches. Major efforts aim to identify novel NB-associated surface molecules that activate immune responses and/or direct drugs to tumor cells and tumor-associated vessels. PVR (Poliovirus Receptor) and B7-H3 are promising targets, since they are expressed by most high-risk NB, are upregulated in tumor vasculature and are essential for tumor survival/invasiveness. PVR is a ligand of DNAM-1 activating receptor that triggers the cytolytic activity of Natural Killer (NK) cells against NB. In animal models targeting of PVR with an attenuated oncolytic poliovirus induced tumor regression and elimination. Also B7-H3 was successfully targeted in preclinical studies and is now being tested in phase I/II clinical trials. B7-H3 down-regulates NK cytotoxicity, providing NB with a mechanism of escape from immune response. The immunosuppressive potential of NB can be enhanced by the release of soluble factors that impair NK cell function and/or recruitment. Among these, TGF-β1 modulates the cytotoxicity receptors and the chemokine receptor repertoire of NK cells.<br/>Here, we summarize the current knowledge on the main cell surface molecules and soluble mediators that modulate the function of NK cells in NB, considering the pros and cons that must be taken into account in the design of novel NK cell-based immunotherapeutic approaches. <br/>http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00056/fullExosomesNeuroblastomaChemokine receptorsnatural killer (NK) cellsTGF-betaanti-tumor immunity |
| spellingShingle | Cristina eBottino Cristina eBottino Alessandra eDondero Francesca eBellora Lorenzo eMoretta Franco eLocatelli Franco eLocatelli Vito ePistoia Alessandro eMoretta Alessandro eMoretta Roberta eCastriconi Roberta eCastriconi Natural Killer Cells and Neuroblastoma: tumor recognition, escape mechanisms and possible novel immunotherapeutic approaches Frontiers in Immunology Exosomes Neuroblastoma Chemokine receptors natural killer (NK) cells TGF-beta anti-tumor immunity |
| title | Natural Killer Cells and Neuroblastoma: tumor recognition, escape mechanisms and possible novel immunotherapeutic approaches |
| title_full | Natural Killer Cells and Neuroblastoma: tumor recognition, escape mechanisms and possible novel immunotherapeutic approaches |
| title_fullStr | Natural Killer Cells and Neuroblastoma: tumor recognition, escape mechanisms and possible novel immunotherapeutic approaches |
| title_full_unstemmed | Natural Killer Cells and Neuroblastoma: tumor recognition, escape mechanisms and possible novel immunotherapeutic approaches |
| title_short | Natural Killer Cells and Neuroblastoma: tumor recognition, escape mechanisms and possible novel immunotherapeutic approaches |
| title_sort | natural killer cells and neuroblastoma tumor recognition escape mechanisms and possible novel immunotherapeutic approaches |
| topic | Exosomes Neuroblastoma Chemokine receptors natural killer (NK) cells TGF-beta anti-tumor immunity |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00056/full |
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