دورية أكاديمية
Critical role of CD206+ macrophages in promoting a cDC1-NK-CD8 T cell anti-tumor immune axis.
| العنوان: | Critical role of CD206+ macrophages in promoting a cDC1-NK-CD8 T cell anti-tumor immune axis. |
|---|---|
| المؤلفون: | Ray A; Department of Pathology, University of California, San Francisco, CA 94143, USA.; ImmunoX Initiative, University of California, San Francisco, CA 94143, USA., Hu KH; Department of Pathology, University of California, San Francisco, CA 94143, USA.; ImmunoX Initiative, University of California, San Francisco, CA 94143, USA., Kersten K; Department of Pathology, University of California, San Francisco, CA 94143, USA.; ImmunoX Initiative, University of California, San Francisco, CA 94143, USA., Courau T; Department of Pathology, University of California, San Francisco, CA 94143, USA.; ImmunoX Initiative, University of California, San Francisco, CA 94143, USA., Kuhn NF; Department of Pathology, University of California, San Francisco, CA 94143, USA.; ImmunoX Initiative, University of California, San Francisco, CA 94143, USA., Zaleta-Linares I; Department of Pathology, University of California, San Francisco, CA 94143, USA.; ImmunoX Initiative, University of California, San Francisco, CA 94143, USA., Samad B; ImmunoX Initiative, University of California, San Francisco, CA 94143, USA.; UCSF CoLabs, University of California, San Francisco, CA 94143, USA., Combes AJ; Department of Pathology, University of California, San Francisco, CA 94143, USA.; ImmunoX Initiative, University of California, San Francisco, CA 94143, USA.; UCSF CoLabs, University of California, San Francisco, CA 94143, USA.; Department of Medicine, University of California, San Francisco, CA 94143, USA., Krummel MF; Department of Pathology, University of California, San Francisco, CA 94143, USA.; ImmunoX Initiative, University of California, San Francisco, CA 94143, USA.; UCSF CoLabs, University of California, San Francisco, CA 94143, USA. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 17. Date of Electronic Publication: 2024 Jun 17. |
| نوع المنشور: | Journal Article; Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Tumor-associated macrophages (TAMs) are frequently categorized as being 'M1' or 'M2' polarized, even as substantial data challenges this binary modeling of macrophage cell state. One molecule consistently referenced as a delineator of a putative immunosuppressive 'M2' state is the surface protein CD206. We thus made a novel conditional CD206 ( Mrc1 ) knock-in mouse to specifically visualize and/or deplete CD206+ 'M2-like' TAMs and assess their correspondence with pro-tumoral immunity. Early, but not late depletion of CD206+ macrophages and monocytes (here, 'Mono/Macs') led to an indirect loss of a key anti-tumor network of NK cells, conventional type I dendritic cells (cDC1) and CD8 T cells. Among myeloid cells, we found that the CD206+ TAMs are the primary producers of CXCL9, and able to differentially attract activated CD8 T cells. In contrast, a population of stress-responsive TAMs ("Hypoxic" or Spp1 +) and immature monocytes, which lack CD206 expression and become prominent following early depletion, expressed markedly diminished levels of CXCL9. Those NK and CD8 T cells which enter CD206-depleted tumors express vastly reduced levels of the corresponding receptor Cxcr3 , the cDC1-attracting chemokine Xcl1 and cDC1 growth factor Flt3l transcripts. Consistent with the loss of this critical network, early CD206+ TAM depletion decreased tumor control by antigen specific CD8 T cells in mice. Likewise, in humans, the CD206 Replete , but not the CD206 Depleted Mono/Mac gene signature correlated robustly with CD8 T cell, NK cell and stimulatory cDC1 gene signatures and transcriptomic signatures skewed towards CD206 Replete Mono/Macs associated with better survival. Together, these findings negate the unqualified classification of CD206+ 'M2-like' macrophages as immunosuppressive by illuminating contexts for their role in organizing a critical tumor-reactive archetype of immunity. Competing Interests: Declaration of Interests: The authors declare no competing interests |
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| معلومات مُعتمدة: | R01 CA197363 United States CA NCI NIH HHS; R37 AI052116 United States AI NIAID NIH HHS; T32 CA108462 United States CA NCI NIH HHS |
| تواريخ الأحداث: | Date Created: 20231114 Latest Revision: 20240628 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC10635006 |
| DOI: | 10.1101/2023.10.31.560822 |
| PMID: | 37961697 |
| قاعدة البيانات: | MEDLINE |
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