Chemotherapy Induces Tumor-Associated Macrophages that Aid Adaptive Immune Responses in Ovarian Cancer

Cancer Immunol Res. 2021 Jun;9(6):665-681. doi: 10.1158/2326-6066.CIR-20-0968. Epub 2021 Apr 10.


Neoadjuvant chemotherapy (NACT) may stimulate anticancer adaptive immune responses in high-grade serous ovarian cancer (HGSOC), but little is known about effects on innate immunity. Using omental biopsies from HGSOC, and omental tumors from orthotopic mouse HGSOC models that replicate the human tumor microenvironment, we studied the impact of platinum-based NACT on tumor-associated macrophages (TAM). We found that chemotherapy reduces markers associated with alternative macrophage activation while increasing expression of proinflammatory pathways, with evidence of inflammasome activation. Further evidence of a shift in TAM functions came from macrophage depletion via CSF1R inhibitors (CSF1Ri) in the mouse models. Although macrophage depletion in established disease had no impact on tumor weight or survival, CSF1Ri treatment after chemotherapy significantly decreased disease-free and overall survival. This decrease in survival was accompanied by significant inhibition of adaptive immune response pathways in the tumors. We conclude that chemotherapy skews the TAM population in HSGOC toward an antitumor phenotype that may aid adaptive immune responses, and therapies that enhance or sustain this during remission may delay relapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / immunology*
  • Cystadenocarcinoma, Serous / mortality
  • Cystadenocarcinoma, Serous / pathology
  • Disease Models, Animal
  • Disease-Free Survival
  • Female
  • Humans
  • Immunity, Innate
  • Mice
  • Mice, Inbred C57BL
  • Neoadjuvant Therapy / methods
  • Neoplasm Grading
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors*
  • Tumor Microenvironment / immunology
  • Tumor-Associated Macrophages / immunology*


  • CSF1R protein, human
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor