Chemosensor receptors are lipid-detecting regulators of macrophage function in cancer
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View abstract on PubMed
Summary
This summary is machine-generated.Chemosensor receptors on tumor-associated macrophages (TAMs) promote cancer growth. Blocking these receptors, like olfactory receptor 51E2 (OR51E2), can lead to cancer regression and boost anti-tumor immunity.
Area Of Science
- Immunology
- Oncology
- Molecular Biology
Background
- Tumor-infiltrating macrophages, or TAMs, are crucial in cancer progression.
- Re-educating TAMs towards an antitumor phenotype is a key immunotherapy strategy.
- Mechanisms of cancer cell influence on TAM education remain largely unknown.
Purpose Of The Study
- To identify novel regulators of TAM phenotype using a genome-wide CRISPR screen.
- To investigate the role of chemosensors in TAM education and cancer progression.
- To explore therapeutic targeting of chemosensors for cancer immunotherapy.
Main Methods
- Unbiased genome-wide CRISPR screen of primary macrophages.
- In vivo deletion of specific chemosensors in TAMs.
- Analysis of human prostate cancer tissues and spatial lipidomics.
Main Results
- Olfactory and vomeronasal receptors (chemosensors) drive a tumor-supportive TAM phenotype.
- Deletion of chemosensors in TAMs led to cancer regression and increased CD8+ T cell infiltration.
- Palmitic acid binding to OR51E2 on TAMs enhances their protumor activity in prostate cancer.
Conclusions
- Chemosensors mediate TAM sensing of the lipid-rich tumor microenvironment.
- Targeting chemosensors represents a promising strategy to enhance antitumor immunity.
- These findings offer new therapeutic avenues for cancer treatment.
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