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

淋巴瘤 癌症研究 抗原 造血 T细胞 淋巴母细胞淋巴瘤 生物 滤泡性淋巴瘤 白血病 免疫疗法 免疫学 免疫系统 干细胞 遗传学
作者
Anita Quintal Gomes,Daniel V. Correia,Ana Rita Grosso,Telma Lança,Cristina Ferreira,João F. Lacerda,João T. Barata,Maria Gomes da Silva,Bruno Silva-Santos
出处
期刊:Haematologica [Ferrata Storti Foundation]
卷期号:95 (8): 1397-1404 被引量:59
标识
DOI:10.3324/haematol.2009.020602
摘要

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.
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