dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Román Alonso, Macarena |
dc.contributor.author | Luque García, Antonio |
dc.contributor.author | Fajardo, Carlos Alberto |
dc.contributor.author | Gros Vidal, Alena |
dc.contributor.author | Arribas López, Joaquin Vicente |
dc.contributor.author | Arenas Lahuerta, Enrique Javier |
dc.contributor.author | Martínez-Sabadell, Alex |
dc.contributor.author | Rius Ruiz, Irene |
dc.contributor.author | Escorihuela Baez, Marta |
dc.date.accessioned | 2022-01-25T12:14:18Z |
dc.date.available | 2022-01-25T12:14:18Z |
dc.date.issued | 2021-02-23 |
dc.identifier.citation | Arenas EJ, Martínez-Sabadell A, Rius Ruiz I, Román Alonso M, Escorihuela M, Luque A, et al. Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation. Nat Commun. 2021 Feb 23;12:1237. |
dc.identifier.issn | 2041-1723 |
dc.identifier.uri | https://hdl.handle.net/11351/6893 |
dc.description | Cancer immunotherapy; Cancer therapeutic resistance |
dc.description.abstract | Immunotherapy has raised high expectations in the treatment of virtually every cancer. Many current efforts are focused on ensuring the efficient delivery of active cytotoxic cells to tumors. It is assumed that, once these active cytotoxic cells are correctly engaged to cancer cells, they will unfailingly eliminate the latter, provided that inhibitory factors are in check. T cell bispecific antibodies (TCBs) and chimeric antigen receptors (CARs) offer an opportunity to test this assumption. Using TCB and CARs directed against HER2, here we show that disruption of interferon-gamma signaling confers resistance to killing by active T lymphocytes. The kinase JAK2, which transduces the signal initiated by interferon-gamma, is a component repeatedly disrupted in several independently generated resistant models. Our results unveil a seemingly widespread strategy used by cancer cells to resist clearance by redirected lymphocytes. In addition, they open the possibility that long-term inhibition of interferon-gamma signaling may impair the elimination phase of immunoediting and, thus, promote tumor progression. |
dc.language.iso | eng |
dc.publisher | Nature Research |
dc.relation.ispartofseries | Nature Communications;12 |
dc.rights | Attribution 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ |
dc.source | Scientia |
dc.subject | Càncer - Immunoteràpia |
dc.subject | Resistència als medicaments |
dc.subject.mesh | Neoplasms |
dc.subject.mesh | /immunology |
dc.subject.mesh | Drug Resistance, Neoplasm |
dc.title | Acquired cancer cell resistance to T cell bispecific antibodies and CAR T targeting HER2 through JAK2 down-modulation |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1038/s41467-021-21445-4 |
dc.subject.decs | neoplasias |
dc.subject.decs | /inmunología |
dc.subject.decs | resistencia a los antineoplásicos |
dc.relation.publishversion | https://doi.org/10.1038/s41467-021-21445-4 |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut Català de la Salut |
dc.contributor.authoraffiliation | [Arenas EJ, Rius Ruiz I] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid 28029, Spain. [Martínez-Sabadell A, Román Alonso M, Escorihuela M, Luque A] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Fajardo CA, Gros A] Tumor Immunology & Immunotherapy Group, VHIO, Barcelona, Spain. [Arribas J] Preclinical Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid 28029, Spain. Tumor Immunology & Immunotherapy Group, VHIO, Barcelona, Spain. Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Barcelona 08003, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain |
dc.identifier.pmid | 33623012 |
dc.identifier.wos | 000623781900011 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |