Assessment of immunological biomarkers in patients with advanced cancer treated by personalized peptide vaccination
Assessment of immunological biomarkers in patients with advanced cancer treated by personalized peptide vaccination
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DOI：
10.4161/cbt.10.12.13448
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发表时间：
2010-12-15
影响因子：
3.6
通讯作者：
Itoh, Kyogo
中科院分区：
文献类型：
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作者：
Noguchi, Masanori;Mine, Takashi;Itoh, Kyogo
为了研究预测个体化多肽疫苗治疗的晚期癌症患者总生存率的免疫生物标志物，对2000年10月至2008年10月接受个体化多肽疫苗接种的500例晚期癌症患者的总生存期与细胞毒性T淋巴细胞(CTL)和免疫球蛋白G(IgG)反应的相关性进行了研究。436例患者中，43例(10%)部分缓解，144例(33%)病情稳定，249例(57%)进展，中位生存期为9.9个月。免疫前淋巴细胞计数(p=0.0095)和对接种多肽的免疫球蛋白反应增强(p=0.0116)，以及表现状态(p<；0.0001)都与总存活率密切相关。为了证实免疫球蛋白应答对CTL应答的优越性，进一步分析了生存超过900天的晚期去势抵抗前列腺癌患者(20例)和300天内死亡的前列腺癌患者(23例)的标本。结果，在长期存活的患者中，观察到对免疫球蛋白应答增强的多肽的数量和免疫球蛋白水平的倍数增加都显著更高(p=0.000282和p=0.00045)。相比之下，CTL反应在两组之间没有统计学差异。因此，淋巴细胞数量和免疫球蛋白反应可作为晚期癌症患者肿瘤疫苗的生物标志物。
To investigate immunological biomarkers to predict overall survival of advanced cancer patients under treatment with personalized peptide vaccination, correlations between overall survival and biomarkers, including cytotoxic T lymphocyte (CTL) and immunoglobulin G (IgG) responses to the vaccinated peptides, were investigated in 500 advanced cancer patients who received a personalized peptide vaccination from October 2000-October 2008. The best clinical response was assessed for in 436 patients, 43 patients (10%) had partial response, 144 patients (33%) had stable disease and 249 patients (57%) had progressive, with a median overall survival of 9.9 months. Both lymphocyte counts prior to the vaccination (p = 0.0095) and increased IgG response (p = 0.0116) to the vaccinated peptides, along with performance status (p < 0.0001), well correlated with overall survival. To confirm the superiority of IgG response to CTL response, the samples from advanced castration-resistant prostate cancer patients who survived more than 900 days (n = 20) and those who died within 300 days (n = 23) were analyzed further. As a result, both the numbers of peptides, to which increased IgG responses were observed, and the fold increases in IgG levels were significantly higher in long-term survivors (p = 0.000282 and p = 0.00045). In contrast, CTL responses were not statistically different between the two groups. Both lymphocyte numbers and IgG response were thus suggested to be biomarkers of cancer vaccine for advanced cancer patients.