Macrophage depletion reduces postsurgical tumor recurrence and metastatic growth in a spontaneous murine model of melanoma

Muly Tham 1, * Karen Khoo 1 Kim Pin Yeo 2 Masashi Kato 3 Amelle Prevost-Blondel 4 Veronique Angeli 2 Jean-Pierre Abastado 5, 1
* Auteur correspondant
1 SIgN - Singapore Immunology Network
2 Department of Microbiology
3 Department of Occupational and Environmental Health
4 UM3 (UMR 8104 / U1016) - Institut Cochin
5 Pole d’innovation thérapeutique en oncologie
Abstract : Surgical resection of tumors is often followed by regrowth at the primary site and metastases may emerge rapidly following removal of the primary tumor. Macrophages are important drivers of tumor growth, and here we investigated their involvement in postoperative relapse as well as explore macrophage depletion as an adjuvant to surgical resection. RETAAD mice develop spontaneous metastatic melanoma that begins in the eye. Removal of the eyes as early as 1 week of age did not prevent the development of metastases; rather, surgery led to increased proliferation of tumor cells locally and in distant metastases. Surgery-induced increase in tumor cell proliferation correlated with increased macrophage density within the tumor. Moreover, macrophages stimulate tumor sphere formation from tumor cells of post-surgical but not control mice. Macrophage depletion with a diet containing the CSF-1R specific kinase inhibitor Ki20227 following surgery significantly reduced postoperative tumor recurrence and abrogated enhanced metastatic outgrowth. Our results confirm that tumor cells disseminate early, and show that macrophages contribute both to post-surgical tumor relapse and growth of metastases, likely through stimulating a population of tumor-initiating cells. Thus macrophage depletion warrants exploration as an adjuvant to surgical resection.
Keywords : Macrophages CSF1R inhibition Postsurgical relapse Tumor-initiating cell
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Article dans une revue
Oncotarget, Impact journals, 2015, [Epub ahead of print]
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Muly Tham, Karen Khoo, Kim Pin Yeo, Masashi Kato, Amelle Prevost-Blondel, et al.. Macrophage depletion reduces postsurgical tumor recurrence and metastatic growth in a spontaneous murine model of melanoma. Oncotarget, Impact journals, 2015, [Epub ahead of print]. 〈inserm-01160364〉

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