Identification and Characterization of Peripheral T-Cell Lymphoma-Associated SEREX Antigens

Peripheral T-cell lymphomas (PTCL) are generally less common and pursue a more aggressive clinical course than B-cell lymphomas, with the T-cell phenotype itself being a poor prognostic factor in adult non-Hodgkin lymphoma (NHL). With notable exceptions such as ALK+ anaplastic large cell lymphoma (ALCL, ALK+), the molecular abnormalities in PTCL remain poorly characterised. We had previously identified circulating antibodies to ALK in patients with ALCL, ALK+. Thus, as a strategy to identify potential antigens associated with the pathogenesis of PTCL, not otherwise specified (PTCL, NOS), we screened a testis cDNA library with sera from four PTCL, NOS patients using the SEREX (serological analysis of recombinant cDNA expression libraries) technique. We identified nine PTCL, NOS-associated antigens whose immunological reactivity was further investigated using sera from 52 B- and T-cell lymphoma patients and 17 normal controls. The centrosomal protein CEP250 was specifically recognised by patients sera and showed increased protein expression in cell lines derived from T-cell versus B-cell malignancies. TCEB3, BECN1, and two previously uncharacterised proteins, c14orf93 and ZBTB44, were preferentially recognised by patients' sera. Transcripts for all nine genes were identified in 39 cancer cell lines and the five genes encoding preferentially lymphoma-recognised antigens were widely expressed in normal tissues and mononuclear cell subsets. In summary, this study identifies novel molecules that are immunologically recognised in vivo by patients with PTCL, NOS. Future studies are needed to determine whether these tumor antigens play a role in the pathogenesis of PTCL.外周T细胞淋巴瘤（Peripheral T-cell Lymphomas, PTCL）通常较B细胞淋巴瘤更为少见，且临床进程更具侵袭性；T细胞表型本身即是成人非霍奇金淋巴瘤（Non-Hodgkin Lymphoma, NHL）的不良预后因素。除ALK阳性间变性大细胞淋巴瘤（ALK+ Anaplastic Large Cell Lymphoma, ALK+ ALCL）等显著例外情况外，PTCL的分子异常特征目前仍未得到充分阐明。我们此前已在ALK+ ALCL患者体内鉴定出针对ALK的循环抗体。因此，为探寻未特指型外周T细胞淋巴瘤（PTCL, Not Otherwise Specified, PTCL, NOS）发病机制相关的潜在抗原，我们采用重组cDNA表达文库的血清学分析（Serological Analysis of Recombinant cDNA Expression Libraries, SEREX）技术，利用4例PTCL, NOS患者的血清对睾丸cDNA文库进行了筛选。我们共鉴定出9个与PTCL, NOS相关的抗原，并使用52例B细胞和T细胞淋巴瘤患者以及17例正常对照的血清进一步研究了这些抗原的免疫反应性。其中，中心体蛋白CEP250可被患者血清特异性识别，且在T细胞恶性肿瘤来源的细胞系中蛋白表达水平高于B细胞恶性肿瘤来源的细胞系。TCEB3、BECN1以及两种此前未被表征的蛋白c14orf93和ZBTB44则可被患者血清优先识别。我们在39株癌细胞系中均检测到这9个基因的转录本，而编码上述优先被淋巴瘤识别的抗原的5个基因在正常组织及单个核细胞亚群中均有广泛表达。综上，本研究鉴定出了可在体内被PTCL, NOS患者免疫系统识别的新型分子。后续仍需开展研究以明确这些肿瘤抗原是否参与PTCL的发病过程。