Experimental and clinical evidence suggests that tumor-associated macrophages (TAMs) play important roles in cancer progression. Here, we have characterized the ontogeny and function of TAM subsets in a mouse model of metastatic ovarian cancer that is representative for visceral peritoneal metastasis. We show that the omentum is a critical premetastatic niche for development of invasive disease in this model and define a unique subset of CD163+ Tim4+ resident omental macrophages responsible for metastatic spread of ovarian cancer cells. Transcriptomic analysis showed that resident CD163+ Tim4+ omental macrophages were phenotypically distinct and maintained their resident identity during tumor growth. Selective depletion of CD163+ Tim4+ macrophages in omentum using genetic and pharmacological tools prevented tumor progression and metastatic spread of disease. These studies describe a specific role for tissue-resident macrophages in the invasive progression of metastatic ovarian cancer. The molecular pathways of cross-talk between tissue-resident macrophages and disseminated cancer cells may represent new targets to prevent metastasis and disease recurrence.
Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer
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Anders Etzerodt, Morgane Moulin, Thomas Koed Doktor, Marcello Delfini, Noushine Mossadegh-Keller, Marc Bajenoff, Michael H. Sieweke, Søren Kragh Moestrup, Nathalie Auphan-Anezin, Toby Lawrence; Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer. J Exp Med 6 April 2020; 217 (4): e20191869. doi: https://doi.org/10.1084/jem.20191869
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