CD206+CD14- Skin-Resident Macrophages and DC-T Cell Clusters Are Spatial Features Characterizing Nonrelapsing...

Area of Science:

• Immunology
• Dermatology
• Oncology

Background:

• Current histopathologic classifications for cutaneous squamous cell carcinoma (cSCC) lack reliability in predicting patient relapse.
• There is a critical need for molecular signatures to stratify cSCC patients during primary tumor resection.

Purpose of the Study:

• To define the immune landscape of primary cSCC and identify molecular signatures that distinguish relapsing from nonrelapsing tumors.
• To discover prognostic biomarkers for cSCC based on immune cell infiltration and spatial interactions.

Main Methods:

• Utilized high-dimensional imaging mass cytometry with a 39-antibody panel on primary cSCC and perilesional skin samples.
• Employed computational analysis of spatially resolved single-cell data to identify distinct immune-cell subsets.
• Conducted spectral flow cytometry on fresh tumor biopsies to assess macrophage phagocytic properties.

Main Results:

• Identified 12 immune-cell subsets differentiating primary cSCC from perilesional skin, including regulatory T cells, CD8+ T lymphocytes, and tumor-associated macrophages in tumors.
• Skin-resident macrophages (CD206+, CD11c+, HLA-DR+, CD14-) infiltrated nonrelapsing tumors more efficiently and showed higher proliferation and cytotoxicity.
• Observed close proximity between dendritic cells (DC-LAMP+) and T lymphocytes in nonrelapsing cSCC, indicating active adaptive immunity.

Conclusions:

• Phagocytic skin-resident macrophages and dendritic cell-T cell clusters are key features distinguishing nonrelapsing cSCC from those at risk of relapse.
• These findings offer potential prognostic biomarkers for cSCC, aiding in patient stratification and treatment decisions.