Qin H, Chen W, Takahashi M, Disis M L, Byrd D R, McCahill L, Bertram K A, Fenton R G, Peace D J, Cheever M A
Department of Medicine, University of Washington, Seattle 98195, USA.
Cancer Res. 1995 Jul 15;55(14):2984-7.
Mutated p21 ras proteins contain single substituted amino acid residues and represent cancer-specific proteins. The current study examined whether primed T cell immunity to mutant p21 ras proteins and/or peptides can be detected in patients with pancreatic or colon cancer. Studies focused on the aspartic acid substitution in amino acid position 12 (denoted D12) as the commonest mutation in gastrointestinal malignancy. Peripheral blood lymphocytes from patients or normal individuals were tested for the ability to proliferate in response to normal or mutated ras peptides or proteins. T-cell responses were defined as a stimulation index of > 2.0. Results showed that 7 of 16 (44%) pancreatic cancer patients responded to ras-D12 peptide. Responses to ras-D12 protein were studied in only the last four patients that responded to D12 peptides. Three of the 4 patients that responded to ras-D12 peptide showed a substantial response to p21 ras-D12 protein (stimulation indices of 12, 8, and 24). Specificity was validated by examining responses to normal and alternate ras peptides and proteins. T-cell responses to ras-D12 peptides were detected in only 2 of 25 (8%) colon cancer patients. None of 11 normal individuals tested had positive responses to normal or mutant ras p21 proteins and/or peptides. Thus, CD4+ T-cell immunity to the mutated segment of ras protein is present in some patients with gastrointestinal cancer.
突变的p21 ras蛋白含有单个取代的氨基酸残基，是癌症特异性蛋白。本研究检测了在胰腺癌或结肠癌患者中是否能检测到对突变型p21 ras蛋白和/或肽的致敏T细胞免疫。研究聚焦于第12位氨基酸的天冬氨酸取代（记为D12），这是胃肠道恶性肿瘤中最常见的突变。检测了患者或正常个体的外周血淋巴细胞对正常或突变的ras肽或蛋白的增殖能力。T细胞反应定义为刺激指数>2.0。结果显示，16例胰腺癌患者中有7例（44%）对ras-D12肽有反应。仅对最后4例对D12肽有反应的患者研究了对ras-D12蛋白的反应。4例对ras-D12肽有反应的患者中有3例对p21 ras-D12蛋白有显著反应（刺激指数分别为12、8和24）。通过检测对正常和替代ras肽及蛋白的反应验证了特异性。在25例结肠癌患者中仅2例（8%）检测到对ras-D12肽的T细胞反应。11例接受检测的正常个体中，无人对正常或突变的ras p21蛋白和/或肽有阳性反应。因此，一些胃肠道癌症患者存在针对ras蛋白突变片段的CD4+ T细胞免疫。
