Background: Development of innovative immunotherapy is imperative to improve the poor survival of the nasopharyngeal carcinoma (NPC) patients. In this study, we evaluated the T cell response to melanoma-associated antigen (MAGE)-A1, MAGE-A3, or synovial sarcoma X-2 (SSX-2) in the peripheral blood of treatment-naive NPC patients. The relationship of responses among the three proteins and the human leukocyte antigen (HLA)-A types were analyzed to provide evidence of designing novel therapy.
Methods: Sixty-one NPC patients admitted into the Tumor Hospital affiliated to the Xinjiang Medical University between March 2015 and July 2016 were enrolled. Mononuclear cells were isolated from the peripheral blood before any treatment. HLA-A alleles were typed with Sanger sequence-based typing technique. The T cell response to the MAGE-A1, MAGE-A3, or SSX-2 was evaluated with the Enzyme-Linked ImmunoSpot assay. Mann-Whitney U-test was used to compare the T cell responses from different groups. Spearman's rank correlation was used to analyze the relationship of T cell responses.
Results: HLA-A*02:01, A*02:07, and A*24:02 were the three most frequent alleles (18.9%, 12.3%, and 11.5%, respectively) among the 22 detected alleles. 31.1%, 19.7%, and 16.4% of the patients displayed MAGE-A1, MAGE-A3, or SSX-2-specific T cell response, respectively. The magnitudes of response to the three proteins were 32.5, 38.0, and 28.7 SFC/106 peripheral blood mononuclear cells, respectively. The T cell response against the three proteins correlated with each other to different extent. The percentage of A*02:01 and A*24:02 carriers were significantly higher in patients responding to any of the three proteins compared to the nonresponders.
Conclusion: MAGE-A1, MAGE-A3, or SSX-2-specific T cell responses were detectable in a subgroup of NPC patients, the frequency and magnitude of which were correlated.
中晚期鼻咽癌患者外周血中HLA-A基因限制性MAGE-A1、MAGE-A3及SSX-2蛋白诱导的T细胞免疫反应初探摘要背景：局部复发和远处转移是鼻咽癌（nasopharyngeal carcinoma, NPC）治疗失败的主要原因，严重影响患者的生存，寻找新的免疫治疗方案意义重大。本研究探讨中晚期NPC初治患者外周血中HLA A限制性MAGE A1、A3及SSX 2抗原肽细胞毒性T细胞(CTL)免疫反应水平，并探讨三者之间的内在联系，为中晚期NPC患者细胞免疫治疗提供实验依据。 方法：选择2015年3月～2016年7月新疆医科大学附属肿瘤医院由病理明确诊断的初治中晚期NPC患者61例，采用SBT sanger法检测患者HLA A等位基因单倍体分型；采用酶联免疫斑点法(ELISPOT)检测经MAGE A1、SSX 2抗原肽刺激后的PBMC分泌IFN γ的CTL细胞的频率及强度。采用Mann Whitney U秩和检验分析患者组间MAGE A1、 MAGE A3、SSX 2反应强度差异，用Spearman's rank correlation进行相关性分析。 结果：61例患者共检测出HLA A等位基因分型22种，其中基因频率前三位的分别是A*02:01（18.9%），A*02:07（12.3%）以及A*24:02（11.5%）。鼻咽癌患者外周血中MAGE A1、MAGE A3及SSX 2抗原特异性CTL免疫应答阳性率分别为31.1%，19.7%和16.4%；平均反应强度分别为32.5，38.0及28.7 SFC/106 PBMC。MAGE A1、MAGE A3与SSX 2之间CTL反应频率与强度均成正相关。MAGE A1、MAGE A3及SSX 2特异性抗原肽阳性反应患者中携带A*02:01（21.1%, 20.8%和25.0%）和A*24:02（18.4%, 25.0%和25.0%）等位基因型的频率较高。 结论：中晚期NPC患者可诱导HLA A限制性MAGE A1、MAGE A3与SSX 2抗原特异性T细胞免疫反应，且彼此间频率与强度具有一定关联性，可能为中晚期NPC患者免疫治疗的临床应用提供实验室依据。.
Keywords: Human Leukocyte Antigen-A; Melanoma-Associated Antigen-A; Nasopharyngeal Carcinoma; Synovial Sarcoma X-2; T Cell Response.