Skip to main content

CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors.

Publication ,  Journal Article
Walens, A; DiMarco, AV; Lupo, R; Kroger, BR; Damrauer, JS; Alvarez, JV
Published in: Elife
April 16, 2019

Over half of breast-cancer-related deaths are due to recurrence 5 or more years after initial diagnosis and treatment. This latency suggests that a population of residual tumor cells can survive treatment and persist in a dormant state for many years. The role of the microenvironment in regulating the survival and proliferation of residual cells following therapy remains unexplored. Using a conditional mouse model for Her2-driven breast cancer, we identify interactions between residual tumor cells and their microenvironment as critical for promoting tumor recurrence. Her2 downregulation leads to an inflammatory program driven by TNFα/NFκB signaling, which promotes immune cell infiltration in regressing and residual tumors. The cytokine CCL5 is elevated following Her2 downregulation and remains high in residual tumors. CCL5 promotes tumor recurrence by recruiting CCR5-expressing macrophages, which may contribute to collagen deposition in residual tumors. Blocking this TNFα-CCL5-macrophage axis may be efficacious in preventing breast cancer recurrence.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

April 16, 2019

Volume

8

Location

England

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Recurrence
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Neoplasm, Residual
  • Mice
  • Macrophages
  • Disease Models, Animal
  • Chemokine CCL5
  • Breast Neoplasms
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Walens, A., DiMarco, A. V., Lupo, R., Kroger, B. R., Damrauer, J. S., & Alvarez, J. V. (2019). CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors. Elife, 8. https://doi.org/10.7554/eLife.43653
Walens, Andrea, Ashley V. DiMarco, Ryan Lupo, Benjamin R. Kroger, Jeffrey S. Damrauer, and James V. Alvarez. “CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors.Elife 8 (April 16, 2019). https://doi.org/10.7554/eLife.43653.
Walens A, DiMarco AV, Lupo R, Kroger BR, Damrauer JS, Alvarez JV. CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors. Elife. 2019 Apr 16;8.
Walens, Andrea, et al. “CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors.Elife, vol. 8, Apr. 2019. Pubmed, doi:10.7554/eLife.43653.
Walens A, DiMarco AV, Lupo R, Kroger BR, Damrauer JS, Alvarez JV. CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors. Elife. 2019 Apr 16;8.

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

April 16, 2019

Volume

8

Location

England

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Recurrence
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Neoplasm, Residual
  • Mice
  • Macrophages
  • Disease Models, Animal
  • Chemokine CCL5
  • Breast Neoplasms