Oral Presentation Australasian Society for Dermatology Research Annual Scientific Meeting 2024

Skin-resident CD169+ macrophages suppress B16F10 melanoma tumour growth in mice (#41)

Yuki Keith 1 , Felix Weninger 1 , Rohit Jain 2 , Shweta Tikoo 2 , Wolfgang Weninger 2 , Tatyana Chtanova 1 , Tri Phan 1
  1. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. Dermatology, Medical University of Vienna, Vienna

Macrophages in the tumour-draining lymph nodes are thought to control primary tumour growth by suppressing tumour-promoting humoral immunity. Here, we investigated the role of macrophages in the syngeneic B16F10 mouse melanoma model. We show that macrophage depletion with the anti-CSF1R monoclonal antibody before, but not after, tumour implantation led to larger tumour volumes. This anti-tumour effect was observed in both wild-type and RAG1-deficient mice, indicating it was independent of T and B cells. We identified CD169+ macrophages in the skin, not the draining lymph node, as the critical cells responsible for this innate immune control of the primary tumour. CD169+ MERTK+LYVE-1+ skin macrophages resided in the deep dermis, dermal white tissue, and adventitia in a steady state skin, and peritumoral areas in the tumour-bearing skin. Dynamic intravital imaging revealed direct ingestion of mCherry-expressing B16F10 cells by LysmKikume-expressing macrophages and the recruitment of highly motile neutrophils into the tumour, which was impaired in anti-CSF1R-treated mice. These data suggest that CD169+ macrophages in the skin, not the draining lymph node, are critical for early innate immune control of skin cancers.