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Neoplastic Immune Mimicry Potentiates Breast Tumor Progression.

Eric B Berens1,2, Sokchea Khou2, Elaine T Huang2

  • 1Department of Anatomy, University of California, San Francisco, San Francisco, California.

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Summary

Breast cancer cells can mimic immune cells, a process called "immune mimicry," to become more aggressive and treatment-resistant. This finding may help predict patient outcomes and stratify cancer care.

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Area of Science:

  • Oncology
  • Cell Biology
  • Immunology

Background:

  • Tumor dedifferentiation enhances cancer cell fitness, increasing aggressiveness and treatment resistance.
  • Cellular plasticity in tumors correlates with poor prognosis and metastasis.
  • Neoplastic cells can adopt non-epithelial characteristics during cancer progression.

Purpose of the Study:

  • To identify and characterize a novel dedifferentiation program in breast cancer cells termed 'immune mimicry.'
  • To investigate the role of immune mimicry in breast cancer aggressiveness, treatment resistance, and metastatic potential.
  • To explore the clinical utility of immune mimicry for patient prognosis and stratification.

Main Methods:

  • Analysis of human breast tumor single-cell RNA-sequencing data and histopathology specimens.
  • In vitro functional experiments using breast cancer cell lines.
  • In vivo studies in murine transgenic and cell line-derived mammary cancer models.
  • Investigated the effect of cytotoxic chemotherapies on epithelial cell dedifferentiation.

Main Results:

  • Subpopulations of dedifferentiated breast cancer cells express leukocyte cell surface receptors, exhibiting 'immune mimicry.'
  • Immune-mimicked cells show dedifferentiation hallmarks and are enriched in treatment-resistant, high-grade tumors.
  • Cytotoxic chemotherapy drives aggressive breast cancer cells toward immune mimicry.
  • Expression of CD69 (a leukocyte activation protein) by neoplastic cells promotes tumor growth.

Conclusions:

  • Neoplastic breast epithelial cells upregulating leukocyte surface receptors contribute to malignancy.
  • Immune mimicry is a dedifferentiation program associated with aggressive breast cancer phenotypes.
  • Immune mimicry holds potential clinical utility for breast cancer patient prognosis and treatment stratification.