Publicação
Identification of a panel of ten cell surface protein antigens associated with immunotargeting of leukemias and lymphomas by peripheral blood γδ T cells
| dc.contributor.author | Gomes, Anita Q. | |
| dc.contributor.author | Correia, Daniel V. | |
| dc.contributor.author | Grosso, Ana R. | |
| dc.contributor.author | Lança, Telma | |
| dc.contributor.author | Ferreira, Cristina | |
| dc.contributor.author | Lacerda, João F. | |
| dc.contributor.author | Barata, João T. | |
| dc.contributor.author | Gomes da Silva, Maria | |
| dc.contributor.author | Silva-Santos, Bruno | |
| dc.date.accessioned | 2012-04-24T13:09:44Z | |
| dc.date.available | 2012-04-24T13:09:44Z | |
| dc.date.issued | 2010-02 | |
| dc.description | ©2010 Ferrata Storti Foundation. This is an open-access paper | eng |
| dc.description.abstract | Background Vγ9Vδ2 T lymphocytes are regarded as promising mediators of cancer immunotherapy due to their capacity to eliminate multiple experimental tumors, particularly within those of hematopoietic origin. However, Vγ9Vδ2 T-cell based lymphoma clinical trials have suffered from the lack of biomarkers that can be used as prognostic of therapeutic success. Design and Methods We have conducted a comprehensive study of gene expression in acute lymphoblastic leukemias and non-Hodgkin’s lymphomas, aimed at identifying markers of susceptibility versus resistance to Vγ9Vδ2 T cell-mediated cytotoxicity. We employed cDNA microarrays and quantitative real-time PCR to screen 20 leukemia and lymphoma cell lines, and 23 primary hematopoietic tumor samples. These data were analyzed using state-of-the-art bioinformatics, and gene expression patterns were correlated with susceptibility to Vγ9Vδ2 T cell mediated cytolysis in vitro. Results We identified a panel of 10 genes encoding cell surface proteins that were statistically differentially expressed between “γδ-susceptible” and “γδ-resistant” hematopoietic tumors. Within this panel, 3 genes (ULBP1, TFR2 and IFITM1) were associated with increased susceptibility to Vγ9Vδ2 T-cell cytotoxicity, whereas the other 7 (CLEC2D, NRP2, SELL, PKD2, KCNK12, ITGA6 and SLAMF1) were enriched in resistant tumors. Furthermore, some of these candidates displayed a striking variance of expression among primary follicular lymphomas and T-cell acute lymphoblastic leukemias. Conclusions Our results suggest that hematopoietic tumors display a highly variable repertoire of surface proteins that can impact on Vγ9Vδ2 cell-mediated immunotargeting. The prognostic value of the proposed markers can now be evaluated in upcoming Vγ9Vδ2 T cell-based lymphoma/leukemia clinical trials. | eng |
| dc.description.sponsorship | This work was supported by the European Molecular Biology Organization (YIP Installation Grant to BS-S),Fundação Calouste Gulbenkian (SDH Oncologia 2008 - Projecto 99293) and Fundação para a Ciência e Tecnologia/FCT (PTDC/BIA-BCM/71663/2006). | eng |
| dc.identifier.citation | Haematologica | 2010; 95(8) | por |
| dc.identifier.issn | 0390-6078 | |
| dc.identifier.uri | http://hdl.handle.net/10451/6154 | |
| dc.identifier.uri | doi:10.3324/haematol.2009.020602 | |
| dc.language.iso | eng | por |
| dc.peerreviewed | yes | por |
| dc.publisher | Ferrata Storti Foundation | por |
| dc.subject | Biomarkers | eng |
| dc.subject | Vγ9Vδ2 T-lymphocytes | eng |
| dc.subject | Hematopoietic tumors | eng |
| dc.subject | Lymphoma cell lines | eng |
| dc.title | Identification of a panel of ten cell surface protein antigens associated with immunotargeting of leukemias and lymphomas by peripheral blood γδ T cells | eng |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | Italy | por |
| oaire.citation.endPage | 1404 | por |
| oaire.citation.startPage | 1397 | por |
| oaire.citation.title | Haematologica | por |
| rcaap.rights | openAccess | por |
| rcaap.type | article | por |