CSF1R-dependent CD169-positive macrophages locally constrain melanoma growth in the skin

Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine

Tissue-resident CSF1R-dependent CD169macrophages localize deep in the skin. They surround growing tumors and directly suppress their growth independent of T and B cells. CD169skin macrophages ingest live tumors, and this phagocytosis is independent of the phosphatidylserine receptor MERTK. teaser Macrophages in the skin reside in multiple distinct layers and perform various functions. Here, we show that CD169macrophages reside in the hypodermis and comprise the major skin myeloid cell population in the steady state. In a syngeneic melanoma model, CD169macrophages encapsulate growing melanomas and directly suppress their growth. CSF1R blockade depleted CD169macrophages in tumors and resulted in unrestrained growth. This local containment of tumor growth in the skin was independent of CD169subcapsular 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 CD169macrophages. This phagocytosis did not require the phosphatidylserine receptor MERTK. CD169macrophages are also enriched in the hypodermis in skin biopsies from healthy human skin and melanoma. These data identify tissue-resident CD169macrophages as a potential cellular target to achieve innate immune containment and reinforce adaptive immune control of tumors.