JCI Insight (Jun 2022)

CD206+ tumor-associated macrophages cross-present tumor antigen and drive antitumor immunity

  • Madhura Modak,
  • Ann-Kathrin Mattes,
  • Daniela Reiss,
  • Wioletta Skronska-Wasek,
  • Rebecca Langlois,
  • Nicolas Sabarth,
  • Renate Konopitzky,
  • Fidel Ramirez,
  • Katharina Lehr,
  • Tobias Mayr,
  • David Kind,
  • Coralie Viollet,
  • Lee Kim Swee,
  • Jutta Petschenka,
  • Karim C. El Kasmi,
  • Elfriede Noessner,
  • Kerstin Kitt,
  • Stefan Pflanz

Journal volume & issue
Vol. 7, no. 11

Abstract

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In many solid cancers, tumor-associated macrophages (TAM) represent the predominant myeloid cell population. Antigen (Ag) cross-presentation leading to tumor Ag–directed cytotoxic CD8+ T cell responses is crucial for antitumor immunity. However, the role of recruited monocyte-derived macrophages, including TAM, as potential cross-presenting cells is not well understood. Here, we show that primary human as well as mouse CD206+ macrophages are effective in functional cross-presentation of soluble self-Ag and non–self-Ag, including tumor-associated Ag (TAA), as well as viral Ag. To confirm the presence of cross-presenting TAM in vivo, we performed phenotypic and functional analysis of TAM from B16-F10 and CT26 syngeneic tumor models and have identified CD11b+F4/80hiCD206+ TAM to effectively cross-present TAA. We show that CD11b+CD206+ TAM represent the dominant tumor-infiltrating myeloid cell population, expressing a unique cell surface repertoire, promoting Ag cross-presentation and Ag-specific CD8+ T cell activation comparable with cross-presenting CLEC9A+ DCs (cDC1). The presence of cross-presenting CD206+ TAM is associated with reduced tumor burden in mouse syngeneic tumor models and with improved overall survival in cutaneous melanoma patients. Therefore, the demonstration of effective Ag cross-presentation capabilities of CD206+ TAM, including their clinical relevance, expands our understanding of TAM phenotypic diversity and functional versatility.

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