Researchers have identified CD169+ macrophages in the deeper layers of the skin that can naturally contain and suppress melanoma growth. The findings suggest these tissue-resident immune cells could be a potential target for strengthening the body’s innate and adaptive immune response to melanoma.
Abstract
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.
Reference:
Yuki Honda Keith, Emily Duchini, Xufeng Lin, Wunna Kyaw, Felix G.P. Weninger, Rama Dhenni, Aiden Josiah Telfser, Abigail K. Grootveld, Deborah Barkauskas, Angela Fontaine-Titley, Shweta Tikoo, Rohit Jain, Wolfgang Weninger, John W. Frew, Elissa K. Deenick, Robert Brink, Linda K. Martin, Tatyana Chtanova, Leonard D. Goldstein, Richard A. Scolyer, Georgina V. Long, Umaimainthan Palendira, Tri Giang Phan; CSF1R-dependent CD169-positive macrophages locally constrain melanoma growth in the skin. J Exp Med 6 July 2026; 223 (7): e20252239. doi: https://doi.org/10.1084/jem.20252239