BMSEHA15
Published online 10 March 2010
(Haematologica 2010, 10.3324/haematol.2009.020602)
Copyright © 2010 by Ferrata Storti Foundation
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Article

Identification of a panel of ten cell surface protein antigens associated with immunotargeting of leukemias and lymphomas by peripheral blood {gamma}{delta}T cells

Anita Q. Gomes1,2,3,*, Daniel V. Correia1,2,*, Ana R. Grosso1, Telma Lança1, Cristina Ferreira4, João F. Lacerda4, João T. Barata1, Maria Gomes da Silva5, Bruno Silva-Santos1,2

1 Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Portugal
2 Instituto Gulbenkian de Ciência, Oeiras, Portugal
3 Escola Superior de Tecnologia da Saúde de Lisboa, Portugal
4 Hospital de Santa Maria - CHLN, Lisboa, Portugal
5 Instituto Português de Oncologia de Lisboa - Francisco Gentil, Portugal

Correspondence: Bruno Silva-Santos, Unidade de Imunologia Molecular, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal. E-mail: bssantos{at}fm.ul.pt.

ABSTRACT

Background: V{gamma}V{delta} 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, V{gamma}V{delta} 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 leukaemias and non-Hodgkin’s lymphomas, aimed at identifying markers of susceptibility versus resistance to V{gamma}V{delta} 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 V{gamma}V{delta} T cell mediated cytolysis in vitro.

Results: We identified a panel of 10 genes encoding cell surface proteins that were statistically differentially expressed between " -susceptible" and " -resistant" hematopoietic tumors. Within this panel, 3 genes (ULBP1, TFR2 and IFITM1) were associated with increased susceptibility V{gamma}V{delta} 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 V{gamma}V{delta} cell-mediated immunotargeting. The prognostic value of the proposed markers can now be evaluated in upcoming V{gamma}V{delta} T cell-based lymphoma/ leukaemia clinical trials.