HLA-A2限制性食管癌特异性突变抗原CTL新表位的鉴定和免疫活性研究

免疫疗法如过继T细胞治疗、CAR-T疗法和免疫检验点抑制剂近年来在临床上取得了显著的治疗效果，研究发现食管癌患者体内存在一些肿瘤特异性突变抗原（TSMA）和突变位点，TSMA为后天突变产生，其免疫原性和组织特异性很强，且其诱导产生的CTLs在抗肿瘤免疫治疗中起着至关重要的作用。此外，不同患者肿瘤基因变异各不相同。因此，鉴定食管癌患者特异性的突变抗原及其自身的突变特异性T淋巴细胞对于食管癌患者的免疫治疗具有重要意义。本研究将对5例HLA-A2+食管患者的正常-肿瘤样本进行高通量测序获得肿瘤特异性突变抗原，运用多种在线预测软件筛选HLA-A2限制性的CTL 新表位（neoepitope），并测定这些表位肽的体外免疫活性。最终筛选若干条食管癌肿瘤特异性突变抗原来源的HLA-A2限制性的突变特异性CTLs新表位，为食管癌基于肿瘤特异性突变的细胞免疫治疗提供新的靶点和方法。

Immunotherapy such as Adoptive T cell therapy, CAR-T therapy and checkpoint blockade made significant therapeutic effect in clinic recently, A lot of studys found that patients with malignant tumors had some Tumour-specific mutant antigen (TSMA), TSMA was acquired mutation, had stronger immunogenicity and tissue specificity, CTLs induced play a critical role in the clinical efficacy. In addition, point mutations evolved gradually, generating extensive clonal diversity. Therefore, identification of antigen specific mutations and its own specific T lymphocytes mutation is of great significance for patients with esophageal cancer immunotherapy. So we undertook the identification of unique HLA-A2 restricted CTL neoepitopes in five HLA-A2+ esophageal cancer (ECs) by using highthroughput sequencing of cDNAs expressed by tumor-normal tissues. The obtained unique HLA-A2 restricted CTL neoepitopes will provide new targets and methods for TSMA specific CD8+T lymphocyte based immune therapy of patients with Esophageal cancer.