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Updated: Dec 19, 2025
Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer
Published on: January 17, 2025
Calreticulin couples with immune checkpoints in pancreatic cancer
Xing Huang1,2,3, Tianyu Tang1,2,3, Xun Wang1,2,3
1Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China.
Abstract:
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.
Insights
Immune checkpoint blockade may not be effective for pancreatic cancer. Instead, targeting calreticulin shows promise for improving anti-tumor immunity and patient survival in pancreatic adenocarcinoma.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Genomics
Background:
- Immune checkpoint blockade is a leading cancer immunotherapy strategy.
- Its efficacy in pancreatic cancer remains uncertain.
- Pancreatic cancer requires novel therapeutic approaches.
Purpose of the Study:
- To evaluate the potential of immune checkpoint blockade in pancreatic cancer.
- To identify alternative therapeutic targets for pancreatic cancer immunotherapy.
- To investigate the role of calreticulin in pancreatic cancer immunity.
Main Methods:
- Analysis of pancreatic cancer datasets from GEPIA2, cBioPortal, and TISIDB.
- Prognostic, genomic, and immunologic analyses of immune checkpoints.
- Assessment of calreticulin expression and its correlation with patient survival and anti-tumor immunity.
Main Results:
- Immune checkpoints are unlikely to be optimal therapeutic targets for pancreatic cancer.
- Calreticulin genomic alterations correlate with immune checkpoints in pancreatic cancer.
- High calreticulin expression is associated with improved overall and disease-free survival in pancreatic adenocarcinoma.
- Calreticulin is linked to enhanced anti-tumor immunity, including immune effector molecules and T-cell signatures.
Conclusions:
- Calreticulin-based therapy offers a more promising avenue for pancreatic cancer immunotherapy than immune checkpoint blockade.
- Calreticulin may serve as a predictive biomarker and therapeutic target for pancreatic cancer.
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