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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Walens, A; DiMarco, AV; Lupo, R; Kroger, BR; Damrauer, JS; Alvarez, JV

Published Date

  • April 16, 2019

Published In

Volume / Issue

  • 8 /

PubMed ID

  • 30990165

Pubmed Central ID

  • PMC6478432

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.43653


  • eng

Conference Location

  • England