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

Daniel Haensel, Bence Daniel, Sadhana Gaddam, Cory Pan, Tania Fabo, Jeremy Bjelajac, Anna R. Jussila, Fernanda Gonzalez, Nancy Yanzhe Li, Yun Chen, JinChao Hou, Tiffany Patel, Sumaira Aasi, Ansuman T. Satpathy and Anthony E. Oro ()
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Daniel Haensel: Stanford University School of Medicine
Bence Daniel: Stanford University School of Medicine
Sadhana Gaddam: Stanford University School of Medicine
Cory Pan: Stanford University School of Medicine
Tania Fabo: Stanford University School of Medicine
Jeremy Bjelajac: Stanford University School of Medicine
Anna R. Jussila: Stanford University School of Medicine
Fernanda Gonzalez: Stanford University School of Medicine
Nancy Yanzhe Li: Stanford University School of Medicine
Yun Chen: Washington University School of Medicine
JinChao Hou: Washington University School of Medicine
Tiffany Patel: Stanford University School of Medicine
Sumaira Aasi: Stanford University School of Medicine
Ansuman T. Satpathy: Stanford University School of Medicine
Anthony E. Oro: Stanford University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-22

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-37993-w

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