Yuki Honda Keith, Emily Duchini, Xufeng Lin, Wunna Kyaw, Felix G.P. Weninger, Rama Dhenni, Aiden Telfser, Abigail K. Grootveld, Deborah Barkauskas, Angela Fontaine-Titley, Shweta Tikoo, Rohit Jain, Wolfgang Weninger, John W. Frew, Elissa K. Deenick, R. van den Brink, Linda K. Martin, Tatyana Chtanova, Leonard D. Goldstein, Richard A. Scolyer, Georgina V. Long, Umaimainthan Palendira, Tri Giang Phan
Macrophages in the skin reside in multiple distinct layers and perform various functions. Here, we show that CD169+ macrophages reside in the hypodermis and comprise the major skin myeloid cell population in the steady state. In a syngeneic melanoma model, CD169+ macrophages encapsulate growing melanomas and directly suppress their growth. CSF1R blockade depleted CD169+ macrophages in tumors and resulted in unrestrained growth. This local containment of tumor growth in the skin was independent of CD169+ subcapsular sinus macrophages in the tumor-draining lymph node and did not require B or T cells. Intravital imaging revealed engulfment and ingestion of live tumor cells by CD169+ macrophages. This phagocytosis did not require the phosphatidylserine receptor MERTK. CD169+ macrophages are also enriched in the hypodermis in skin biopsies from healthy human skin and melanoma. These data identify tissue-resident CD169+ macrophages as a potential cellular target to achieve innate immune containment and reinforce adaptive immune control of tumors.