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Macrophage-Targeting by CSF1/1R Blockade in Pancreatic Cancers
Won Jin Ho1, Elizabeth M Jaffee1
1Skip Viragh Center for Pancreatic Cancer, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Medicine, Baltimore, Maryland. wjho@jhmi.edu ejaffee@jhmi.edu.
Abstract:
Published in Cancer Research in 2014, Zhu and colleagues achieved a mechanistic leap in our understanding of cancer-associated macrophage biology with their proof-of-concept study showing that macrophage-specific targeting, via blocking colony-stimulating factor-1 (CSF1) signaling through its cognate receptor CSF1R, synergized with checkpoint immunotherapy to enhance antitumor immunity in mouse models of pancreatic cancer. Here, we reflect on the critical set of observations presented in this study and how the study's findings fueled the subsequent efforts to translate CSF1/1R-specific and other tumor-associated macrophage modulating therapies into the clinic.See related article by Zhu and colleagues, Cancer Res 2014;74:5057-69.
Insights
Blocking colony-stimulating factor-1 (CSF1) signaling via CSF1R enhanced pancreatic cancer immunotherapy in mice. This study
Area of Science:
- Immunology
- Oncology
- Cancer Biology
Background:
- Tumor-associated macrophages (TAMs) play a critical role in cancer progression.
- Targeting TAMs is a promising strategy for cancer therapy.
Purpose of the Study:
- To investigate the efficacy of blocking colony-stimulating factor-1 (CSF1) signaling in combination with checkpoint immunotherapy.
- To enhance antitumor immunity in pancreatic cancer mouse models.
Main Methods:
- Macrophage-specific targeting by blocking CSF1/CSF1R signaling.
- Combination therapy with checkpoint immunotherapy.
- Evaluation in mouse models of pancreatic cancer.
Main Results:
- Blocking CSF1/CSF1R signaling synergized with checkpoint immunotherapy.
- Enhanced antitumor immunity was observed.
- Proof-of-concept for targeting TAMs in pancreatic cancer.
Conclusions:
- Macrophage-targeting therapies, specifically CSF1/1R inhibition, can enhance immunotherapy efficacy.
- This study provides a foundation for translating TAM-modulating therapies into clinical practice for pancreatic cancer.
