Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage III colorectal cancer.
Cytotoxic T lymphocyte response to peptide vaccination predicts survival in stage III colorectal cancer.
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DOI：
10.1111/cas.13547
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发表时间：
2018-05
期刊：
影响因子：
5.7
通讯作者：
Okuno K
中科院分区：
文献类型：
--
作者：
Kawamura J;Sugiura F;Sukegawa Y;Yoshioka Y;Hida JI;Hazama S;Okuno K
我们之前报道了一项关于肽疫苗环指蛋白43（RNF 43）和线粒体外膜34-kDa转位酶（TOMM 34）联合尿嘧啶-替加氟（UFT）/LV治疗转移性结直肠癌（CRC）患者的I期临床试验，并证明了这种联合治疗的安全性和免疫反应性。在本研究中，我们评价了疫苗接种诱导的免疫应答，以阐明联合治疗作为辅助治疗的生存获益。我们最初以HLA-掩蔽的方式招募了44名患者。HLA公开后，28例患者为HLA-A *2402-匹配组，16例为不匹配组。在HLA匹配组中，14名患者在2个周期的治疗后具有对RNF 43和/或TOMM 34肽特异性的阳性CTL应答，9名具有阴性应答;在HLA不匹配组中，10名CTL应答为阳性，2名为阴性。在HLA匹配组中，阳性CTL亚组的3年无复发生存率（RFS）显著优于阴性应答亚组。接种疫苗诱导的CTL应答阴性的患者显示出RFS比阳性应答患者更短的显著趋势。此外，在HLA不匹配组中，阳性CTL应答亚组显示出与HLA匹配组同样良好的3年RFS。总之，疫苗接种诱导的CTL对肽疫苗接种的应答可以预测III期CRC在佐剂环境中的存活率。
We previously reported a phase I clinical trial of a peptide vaccine ring finger protein 43 (RNF43) and 34‐kDa translocase of the outer mitochondrial membrane (TOMM34) combined with uracil‐tegafur (UFT)/LV for patients with metastatic colorectal cancer (CRC), and demonstrated the safety and immunological responsiveness of this combination therapy. In this study, we evaluated vaccination‐induced immune responses to clarify the survival benefit of the combination therapy as adjuvant treatment. We enrolled 44 patients initially in an HLA‐masked fashion. After the disclosure of HLA, 28 patients were in the HLA‐A*2402‐matched and 16 were in the unmatched group. In the HLA‐matched group, 14 patients had positive CTL responses specific for the RNF43 and/or TOMM34 peptides after 2 cycles of treatment and 9 had negative responses; in the HLA‐unmatched group, 10 CTL responses were positive and 2 negative. In the HLA‐matched group, 3‐year relapse‐free survival (RFS) was significantly better in the positive CTL subgroup than in the negative‐response subgroup. Patients with negative vaccination‐induced CTL responses showed a significant trend towards shorter RFS than those with positive responses. Moreover, in the HLA‐unmatched group, the positive CTL response subgroup showed an equally good 3‐year RFS as in the HLA‐matched group. In conclusion, vaccination‐induced CTL response to peptide vaccination could predict survival in the adjuvant setting for stage III CRC.
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DOI：
10.1093/annonc/mdu232
发表时间：
2014-09
期刊：
Annals of oncology : official journal of the European Society for Medical Oncology
影响因子：
--
作者：
Yoshida M;Ishiguro M;Ikejiri K;Mochizuki I;Nakamoto Y;Kinugasa Y;Takagane A;Endo T;Shinozaki H;Takii Y;Mochizuki H;Kotake K;Kameoka S;Takahashi K;Watanabe T;Watanabe M;Boku N;Tomita N;Nakatani E;Sugihara K;ACTS-CC study group
通讯作者：
ACTS-CC study group
影响因子：
45.3
作者：
Kuebler, J. Philip;Wieand, H. Samuel;Wolmark, Norman
通讯作者：
Wolmark, Norman
影响因子：
158.5
作者：
Twelves, C;Wong, A;Scheithauer, W
通讯作者：
Scheithauer, W
影响因子：
11.5
作者：
Uchida, N;Tsunoda, T;Tahara, H
通讯作者：
Tahara, H
影响因子：
45.3
作者：
Douillard, JY;Hoff, PM;Benner, SE
通讯作者：
Benner, SE