Immunohistological analysis of pancreatic carcinoma after vaccination with survivin 2B peptide: Analysis of an autopsy series.
Immunohistological analysis of pancreatic carcinoma after vaccination with survivin 2B peptide: Analysis of an autopsy series.
复制标题
接种生存素 2B 肽后胰腺癌的免疫组织学分析：尸检系列分析。
DOI：
10.1111/cas.14099
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Torigoe T.
中科院分区：
文献类型：
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作者：
Kubo T;Tsurita G;Hirohashi Y;Yasui H;Ota Y;Watanabe K;Murai A;Matsuo K;Asanuma H;Shima H;Wada S;Nakatsugawa M;Kanaseki T;Tsukahara T;Mizuguchi T;Hirata K;Takemasa I;Imai K;Sato N;Torigoe T.
免疫检查点抑制剂（ICI）通过在现有疗法之外提供新的选择，彻底改变了癌症的治疗。然而，由于抗原特异性，肽疫苗接种疗法仍然代表有吸引力的方法。我们鉴定了生存素2B肽（SVN-2B），一种由生存素编码的9聚体抗原肽，并进行了一项基于SVN-2B肽疫苗的II期随机临床试验，靶向不可切除和难治性胰腺癌。SVN-2B肽疫苗在该研究中没有任何统计学显著的临床益处。因此，我们进行了尸检研究，以分析免疫状态的胰腺癌病变的组织学水平。对13名死于胰腺癌的患者进行尸检，其中7名接受SVN-2B肽疫苗接种，6名未接受疫苗接种，作为阴性对照。免疫组化染色分析免疫相关分子的表达。通过四聚体染色和酶联免疫斑点试验分析细胞毒性T淋巴细胞。组织学分析显示，在接受SVN-2B肽疫苗的患者中，CD 8 +T细胞在一些病变中密集浸润。在这些病例中观察到癌细胞中程序性细胞死亡配体1的高表达率，表明CTL由SVN-2B肽疫苗接种诱导并已浸润病变。缺乏显著的抗肿瘤作用最可能归因于免疫检查点分子的表达。这些发现表明，肿瘤特异性肽疫苗和ICI的组合可能是未来治疗胰腺癌的一种有前途的方法。
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer by providing new options in addition to existing therapies. However, peptide vaccination therapies still represent an attractive approach, because of the antigen specificity. We identified survivin 2B peptide (SVN‐2B), a 9‐mer antigenic peptide encoded by survivin, and an SVN‐2B peptide vaccine‐based phase II randomized clinical trial targeting unresectable and refractory pancreatic carcinoma was undertaken. The SVN‐2B peptide vaccine did not have any statistically significant clinical benefits in that study. Therefore, we undertook an autopsy study to analyze the immune status of the pancreatic cancer lesions at the histological level. Autopsies were carried out in 13 patients who had died of pancreatic cancer, including 7 who had received SVN‐2B peptide vaccination and 6 who had not, as negative controls. The expression of immune‐related molecules was analyzed by immunohistochemical staining. Cytotoxic T lymphocytes were analyzed by tetramer staining and enzyme‐linked immunospot assay. Histological analysis revealed dense infiltration of CD8+T cells in some lesions in patients who had received the SVN‐2B peptide vaccine. A high rate of programmed cell death ligand 1 expression in cancer cells was observed in these cases, indicating that CTLs were induced by SVN‐2B peptide vaccination and had infiltrated the lesions. The lack of a significant antitumor effect was most likely attributable to the expression of immune checkpoint molecules. These findings suggest that the combination of a tumor‐specific peptide vaccine and an ICI might be a promising approach to the treatment of pancreatic carcinoma in the future.