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.