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Updated: Dec 29, 2025
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Using CRISPR/Cas9 Gene Editing to Investigate the Oncogenic Activity of Mutant Calreticulin in Cytokine Dependent Hematopoietic Cells
Published on: January 5, 2018
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Secreted calreticulin mutants subvert anticancer immunosurveillance.
Peng Liu1,2,3,4,5,6, Liwei Zhao1,2,3,4,5,6, Guido Kroemer1,2,3,4,5,7,8,9
1Equipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.
Oncoimmunology
|February 1, 2020
Summary
Mutant calreticulin (CALR) proteins are secreted, promoting myeloproliferative diseases and suppressing anti-cancer immune responses by inhibiting dendritic cell phagocytosis.
Area of Science:
- Molecular Biology
- Immunology
- Oncology
Background:
- Mutations in the calreticulin (CALR) gene lead to C-terminal KDEL motif loss, causing CALR secretion.
- These CALR mutants are implicated in myeloproliferative diseases through thrombopoietin receptor activation.
- Extracellular CALR impairs the immune system's ability to clear dying cancer cells.
Discussion:
- The RUSH technology was used to track CALR trafficking, confirming the secretion of truncated CALR variants.
- Secreted CALR inhibits phagocytosis of apoptotic cancer cells by dendritic cells (DCs).
- This immunosuppressive mechanism reduces the effectiveness of cancer immunotherapies.
Key Insights:
- CALR mutations drive both cancer development and immune evasion.
- Secreted CALR acts as an immunosuppressive factor, hindering anti-tumor immunity.
- The study links CALR's role in myeloproliferative neoplasms to its impact on anti-cancer immunity.
Outlook:
- Further research into targeting extracellular CALR could enhance cancer immunotherapy efficacy.
- Understanding CALR's dual role may lead to novel therapeutic strategies for myeloproliferative diseases and cancer.
- Investigating the precise mechanisms of CALR-mediated immunosuppression is crucial.
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