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Contribution of annexin A1 to anticancer immunosurveillance

Elisa Elena Baracco1,2, Gautier Stoll1,2, Peter Van Endert3

  • 1Institut de Cancérologie, Gustave Roussy Cancer Campus (GRCC), Villejuif, France.

Oncoimmunology
|September 14, 2020
PubMed

Insights

Cancers lacking annexin A1 (ANXA1) resist chemotherapy due to reduced calreticulin (CALR) exposure. Restoring CALR levels can re-sensitize ANXA1-deficient tumors to chemotherapy, suggesting CALR as a potential immunotherapy target for immune-escaping cancers.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • Annexin A1 (ANXA1) expression is crucial for immunogenic chemotherapies' efficacy.
  • ANXA1 facilitates dendritic cell (DC) synapse formation with dying cancer cells via formyl peptide receptor-1 (FPR1).
  • ANXA1 downregulation is observed in various human carcinomas.

Purpose of the Study:

  • To investigate the role of ANXA1 in cancer cell antigen presentation to DCs.
  • To explore the potential of calreticulin (CALR) as a therapeutic agent in ANXA1-deficient cancers.

Main Methods:

  • Analysis of ANXA1-deficient mouse cancer models.
  • Assessment of calreticulin (CALR) exposure on dying cancer cells.
  • Evaluation of DC phagocytic uptake of dead-cell antigens.
  • Intratumoral administration of recombinant CALR protein in chemotherapy-treated mice.
  • Analysis of tumor-infiltrating immune cells in human ANXA1-low cancers.

Main Results:

  • ANXA1-deficient cancer cells show impaired exposure of the 'eat-me' signal, CALR.
  • Recombinant CALR protein restored the response of ANXA1-deficient cancers to anthracycline chemotherapy.
  • ANXA1-low human cancers (breast, colorectal, lung, kidney) exhibit reduced infiltration of DCs and cytotoxic T lymphocytes.
  • ANXA1 deficiency correlates with immune escape in carcinomas.

Conclusions:

  • ANXA1 plays a critical role in facilitating the immunogenic cell death and subsequent DC phagocytosis through CALR exposure.
  • Restoring CALR levels can overcome chemotherapy resistance in ANXA1-deficient tumors.
  • ANXA1-low cancers may be susceptible to local immunotherapy strategies involving CALR protein to enhance anti-tumor immunity.
Keywords:
Calreticulinchemotherapyimmunogenic cell deathimmunotherapyprognostic markerstumor immune infiltrate

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