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Intratumoral immunosuppression profiles in 11q-deleted neuroblastomas provide new potential therapeutic targets

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Intratumoral immunosuppression profiles in 11q-deleted neuroblastomas provide new potential therapeutic targets

dc.contributor.author	Coronado, Esther
dc.contributor.author	Yañez Peralta, Yania
dc.contributor.author	Vidal, Enrique
dc.contributor.author	Rubio, Luis
dc.contributor.author	Vera Sempere, Francisco José
dc.contributor.author	Cañada Martinez, Antonio José
dc.contributor.author	Panadero, Joaquin
dc.contributor.author	Cañete Nieto, Adela
dc.contributor.author	Ladenstein, Ruth
dc.contributor.author	Castel Sánchez, Victoria
dc.contributor.author	Font de Mora Sainz, Jaime
dc.date.accessioned	2022-06-10T07:46:29Z
dc.date.available	2022-06-10T07:46:29Z
dc.date.issued	2021
dc.identifier.citation	Coronado, Esther Yañez Peralta, Yania Vidal, Enrique Rubio, Luis Vera Sempere, Francisco José Cañada Martinez, Antonio José Panadero, Joaquin Cañete Nieto, Adela Ladenstein, Ruth Castel Sánchez, Victoria Font de Mora Sainz, Jaime 2021 Intratumoral immunosuppression profiles in 11q-deleted neuroblastomas provide new potential therapeutic targets Molecular Oncology 15 2 364 380
dc.identifier.uri	https://hdl.handle.net/10550/83095
dc.description.abstract	High‐risk neuroblastoma (NB) patients with 11q deletion frequently undergo late but consecutive relapse cycles with fatal outcome. To date, no actionable targets to improve current multi‐modal treatment have been identified. We analyzed immune microenvironment and genetic profiles of high‐risk NB correlating with 11q immune status. We show in two independent cohorts that 11q‐deleted NB exhibit various immune‐inhibitory mechanisms, including increased CD4+ resting T cells and M2 macrophages, higher expression of programmed death‐ligand 1, interleukin‐10, transforming growth factor‐beta‐1 and indoleamine 2,3‐dioxygenase 1 (P<0.05), and also higher chromosomal breakages (P≤0.02) and hemizygosity of immunosuppressive miRNAs than MYCN‐amplified and other 11q‐non‐deleted high‐risk NB. We also analyzed benefits of maintenance treatment in 83 high‐risk stage M NB patients focusing on 11q status, either with standard anti‐GD2 immunotherapy (n=50) or previous retinoic acid‐based therapy alone (n=33). Immunotherapy associated with higher EFS (50 vs. 30, P=0.028) and OS (72 vs. 52, P=0.047) at 3 years in the overall population. Despite benefits from standard anti‐GD2 immunotherapy in high‐risk NB patients, those with 11q deletion still face poor outcome. This NB subgroup displays intratumoral immune suppression profiles, revealing a potential therapeutic strategy with combination immunotherapy to circumvent this immune checkpoint blockade.
dc.language.iso	eng
dc.relation.ispartof	Molecular Oncology, 2021, vol. 15, num. 2, p. 364-380
dc.subject	Patologia
dc.title	Intratumoral immunosuppression profiles in 11q-deleted neuroblastomas provide new potential therapeutic targets
dc.type	journal article	es_ES
dc.date.updated	2022-06-10T07:46:29Z
dc.identifier.doi	10.1002/1878-0261.12868
dc.identifier.idgrec	141943
dc.rights.accessRights	open access	es_ES