Calreticulin couples with immune checkpoints in pancreatic cancer
Calreticulin couples with immune checkpoints in pancreatic cancer
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DOI：
10.1002/ctm2.10
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发表时间：
2020-04-18
影响因子：
10.6
通讯作者：
Liang, Tingbo
中科院分区：
文献类型：
--
作者：
Huang, Xing;Tang, Tianyu;Liang, Tingbo
尽管免疫检查点阻断被认为是未来癌症免疫治疗的主要方法，但它是否适用于胰腺癌仍是未知数。为了解决这个问题，胰腺癌相关数据集分别由基因表达谱交互分析2（GEPIA2），cBioPortal和肿瘤和免疫系统相互作用数据库（TISIDB）收集，随后对所有完善的免疫检查点进行预后，基因组和免疫学分析。结果表明，免疫检查点可能不是胰腺癌治疗的理想靶点。有趣的是，钙网蛋白的基因组改变，化疗诱导的癌症免疫原性细胞死亡的关键介质，被发现与胰腺癌的免疫检查点耦合。此外，观察到钙网蛋白在胰腺癌中高表达，并且钙网蛋白高表达显著有利于胰腺癌患者的总生存期和无病生存期。重要的是，钙网蛋白进一步被揭示与胰腺癌中的抗肿瘤免疫密切相关，包括多种免疫效应分子和T细胞特征。综上所述，基于钙网蛋白的治疗可能代表了比免疫检查点阻断治疗更有前途的胰腺癌免疫治疗前景。
Although immune checkpoint blockade is considered to be the dominant approach in future cancer immunotherapy, whether it will apply to pancreatic cancer remains largely unknown. To address this issue, pancreatic cancer-associated datasets were individually collected by Gene Expression Profiling Interactive Analysis 2 (GEPIA2), cBioPortal, and Tumor and Immune System Interaction Database (TISIDB), and subsequently subjected to prognostic, genomic, and immunologic analyses of all well-established immune checkpoints. The results indicate that immune checkpoints might not be ideal targets for pancreatic cancer therapy. Intriguingly, the genomic alteration of calreticulin, the key mediator of chemotherapy-induced cancer immunogenic cell death, was found to couple with immune checkpoints in pancreatic cancer. Moreover, calreticulin was observed to be highly expressed in pancreatic adenocarcinoma, and high calreticulin expression significantly favors both overall survival and disease-free survival of patients with pancreatic adenocarcinoma. Importantly, calreticulin was further revealed to be closely related to anti-tumor immunity in pancreatic adenocarcinoma, including multiple immune effector molecules and T-cell signatures. Taken together, calreticulin-based therapy may represent a more promising prospect for pancreatic cancer immunotherapy than immune checkpoint blockade therapy.