Calreticulin couples with immune checkpoints in pancreatic cancer

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.