2. Academic Validation
  3. Skin basal cell carcinomas assemble a pro-tumorigenic spatially organized and self-propagating Trem2+ myeloid niche

Skin basal cell carcinomas assemble a pro-tumorigenic spatially organized and self-propagating Trem2+ myeloid niche

  • Nat Commun. 2023 May 10;14(1):2685. doi: 10.1038/s41467-023-37993-w.
Daniel Haensel 1 2,  Bence Daniel 3 4,  Sadhana Gaddam 1 2,  Cory Pan 1 2,  Tania Fabo 1,  Jeremy Bjelajac 1,  Anna R Jussila 1 2,  Fernanda Gonzalez 1 2,  Nancy Yanzhe Li 1 2,  Yun Chen 5 6,  JinChao Hou 5,  Tiffany Patel 1 2,  Sumaira Aasi 2,  Ansuman T Satpathy 3 4 7,  Anthony E Oro 8 9
Affiliations

Affiliations

  • 1 Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
  • 2 Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA.
  • 3 Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
  • 4 Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, 94158, USA.
  • 5 Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
  • 6 Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.
  • 7 Parker Institute of Cancer Immunotherapy, San Francisco, CA, 94305, USA.
  • 8 Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
  • 9 Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA. [email protected].
PMID: 37164949 DOI: 10.1038/s41467-023-37993-w
Abstract

Cancer immunotherapies have revolutionized treatment but have shown limited success as single-agent therapies highlighting the need to understand the origin, assembly, and dynamics of heterogeneous tumor immune niches. Here, we use single-cell and imaging-based spatial analysis to elucidate three microenvironmental neighborhoods surrounding the heterogeneous basal cell carcinoma tumor epithelia. Within the highly proliferative neighborhood, we find that TREM2+ skin cancer-associated macrophages (SCAMs) support the proliferation of a distinct tumor epithelial population through an immunosuppression-independent manner via oncostatin-M/JAK-STAT3 signaling. SCAMs represent a unique tumor-specific TREM2+ population defined by VCAM1 surface expression that is not found in normal homeostatic skin or during wound healing. Furthermore, SCAMs actively proliferate and self-propagate through multiple serial tumor passages, indicating long-term potential. The tumor rapidly drives SCAM differentiation, with intratumoral injections sufficient to instruct naive bone marrow-derived monocytes to polarize within days. This work provides mechanistic insights into direct tumor-immune niche dynamics independent of immunosuppression, providing the basis for potential combination tumor therapies.

Figures
Products