Characterization of tumor antigen peptide-specific T cells isolated from the neoplastic tissue of patients with gastric adenocarcinoma
Characterization of tumor antigen peptide-specific T cells isolated from the neoplastic tissue of patients with gastric adenocarcinoma
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DOI：
10.1007/s00262-009-0693-8
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发表时间：
2009-11-01
影响因子：
5.8
通讯作者：
D'Elios, Mario Milco
中科院分区：
文献类型：
--
作者：
Amedei, Amedeo;Niccolai, Elena;D'Elios, Mario Milco
胃癌是世界范围内发病率和死亡率的重要原因。手术切除仍然是胃腺癌的主要根治性治疗，但5年生存率低（15-35%），促使许多新的治疗策略，如特异性免疫治疗的研究。本研究的目的是分析胃腺癌患者T细胞对不同胃癌相关抗原肽反应的功能特性。为此，我们克隆和表征肿瘤浸润性T细胞（TILs）从肿瘤性胃组织样本中分离。在20名患者中有17名记录了对所测试的胃癌抗原的不同肽的特异性T细胞应答，所述患者是根据其HLA-A02和/或-A24等位基因选择的。大多数癌肽特异性TIL表达Th 1/Tc 1特征和对靶细胞的细胞毒活性。还研究了从相同患者的外周血获得的癌肽特异性T细胞的效应子功能。大多数外周血肽特异性T细胞也表达Th 1/Tc 1功能谱。总之，在大多数胃腺癌患者中，可检测到特异性1型T细胞对胃癌抗原的反应，并有可能阻碍肿瘤细胞生长。然而，为了在体内获得肿瘤细胞杀伤，可能需要通过接种适当的癌症抗原肽或通过注射体外扩增的自体肿瘤肽特异性T细胞来增强癌症肽特异性Th 1/Tc 1细胞的活性和数量。
Gastric cancer is a significant cause of morbidity and mortality worldwide. Surgical resection remains the primary curative treatment for gastric adenocarcinoma, but the poor (15-35%) survival rate at 5 years has prompted many studies for new therapeutic strategies, such as specific immunotherapy. The aim of this study was to analyze the functional properties of the T cell response to different antigen peptides related to gastric cancer in patients with gastric adenocarcinoma. To this purpose, we have cloned and characterized tumor-infiltrating T cells (TILs) isolated from the neoplastic gastric tissue samples. A T cell response specific to different peptides of gastric cancer antigens tested was documented in 17 out of 20 patients, selected for their HLA-A02 and/or -A24 alleles. Most of the cancer peptide-specific TILs expressed a Th1/Tc1 profile and cytotoxic activity against target cells. The effector functions of cancer peptide-specific T cells obtained from the peripheral blood of the same patients were also studied. The majority of peripheral blood peptide-specific T cells also expressed the Th1/Tc1 functional profile. In conclusion, in most of the patients with gastric adenocarcinoma, a specific type-1 T cell response to gastric cancer antigens was detectable and would have the potential of hamper tumor cell growth. However, in order to get tumor cell killing in vivo, the activity and the number of cancer peptide-specific Th1/Tc1 cells probably need to be enhanced by vaccination with the appropriate cancer antigenic peptides or by injection of the autologus tumor peptide-specific T cells expanded in vitro.