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

Area of Science:

• Cancer Biology
• Immunology
• Dermatology

Background:

• Cancer immunotherapies have advanced treatment but often require combination strategies.
• Understanding tumor immune niches is crucial for improving therapeutic efficacy.
• Heterogeneity within tumor microenvironments influences treatment outcomes.

Purpose of the Study:

• To elucidate the origin, assembly, and dynamics of tumor immune niches in basal cell carcinoma.
• To identify specific immune cell populations and their interactions within the tumor microenvironment.
• To uncover mechanisms of tumor cell proliferation driven by immune cells.

Main Methods:

• Single-cell analysis
• Imaging-based spatial analysis
• Characterization of tumor-associated macrophages (TAMs)
• In vivo tumor models

Main Results:

• Identified three distinct microenvironmental neighborhoods in basal cell carcinoma.
• Discovered TREM2+ skin cancer-associated macrophages (SCAMs) supporting tumor epithelial proliferation via oncostatin-M/JAK-STAT3 signaling.
• Demonstrated that SCAMs are a unique, tumor-specific TREM2+ population expressing VCAM1, capable of self-propagation and rapid differentiation from monocytes.

Conclusions:

• SCAMs promote tumor proliferation through an immunosuppression-independent mechanism.
• SCAMs represent a novel, persistent immune cell population within the tumor microenvironment.
• These findings provide mechanistic insights into tumor-immune interactions and suggest potential combination therapy strategies.