Immune Marker Profiles Distinguish cSCC From BCC in Tumor Microenvironment Study
Key Clinical Summary
- Cutaneous squamous cell carcinoma (cSCC) samples showed significantly higher stromal labeling indices for CD4, CD8, Foxp3, CD68, CD163, and CD11c compared with basal cell carcinoma (BCC) (P < .050).
- Immune marker expression was consistently greater at the invasive front than in the tumor core for both tumor types.
- Several immune markers in cSCC correlated with clinicopathological factors, including T status, N status, infiltration depth, and prior tumor history.
A tissue microarray analysis provides a detailed characterizations of the tumor microenvironment (TME) differences between BCC and cSCC. The study builds on prior work examining immune infiltration and immune checkpoint expression in nonmelanoma skin cancers. Findings highlight distinct immune cell patterns involving T-cell subsets and macrophage-related markers across tumor regions.
Study Findings
Researchers evaluated immune marker expression and spatial distribution of CD4, CD8, Foxp3, CD68, CD163, and CD11c in both the invasive front and tumor core of BCC and cSCC using chromogenic immunohistochemistry. Quantification via QuPath showed significantly higher stromal labeling indices for all markers in cSCC compared with BCC (CD4**, CD8*, Foxp3*, CD68*, CD163**, CD11c*; *P < .001; **P < .050).
Notably, macrophage-associated ratios CD163/CD68 (P < .001) and CD163/CD11c (P = .001) were markedly elevated in cSCC, suggesting a distinct polarization pattern within its TME. Across both cancers, the invasive front exhibited higher immune marker expression than the tumor core when statistical significance was reached, underscoring the biological importance of this region in tumor–immune interactions.
Several associations emerged between immune marker expression and clinicopathologic variables in cSCC. CD4 correlated with T status (P = .011), CD11c with N status (P = .041), and CD68 with depth of infiltration (P = .018). CD8 and CD11c were also associated with previous tumor occurrence (P = .006 and P = .029, respectively).
The authors note the growing clinical urgency: Although mortality rates for nonmelanoma skin cancers are relatively low, global deaths reached 63 731 in 2020—comparable to melanoma—reflecting their high incidence. The researchers emphasize the need for deeper profiling of the pro- and anti-inflammatory features of these TMEs to better understand their clinical relevance and implications for immunotherapy.
Clinical Implications
These findings reinforce cSCC’s status as a more immunologically active tumor than BCC, with significantly higher infiltration of T cells and macrophage-related populations. The prominence of marker expression at the invasive front suggests this region could serve as a critical site for diagnostic scoring or therapeutic targeting.
For clinicians and managed care stakeholders, the correlations between immune markers and disease characteristics—including nodal involvement, tumor stage, and infiltration depth—may help refine risk stratification frameworks. As immunotherapies expand in dermatologic oncology, detailed characterization of TME components may support predictive modeling, sharper patient selection, and the development of novel therapeutic strategies.
The authors note that the study “provides a comprehensive analysis of the TME of BCC and cSCC, emphasizing the distinct expression patterns of the TME with regard to T cell- and macrophage-associated markers.”
Conclusion
This analysis underscores key immunologic distinctions between BCC and cSCC, particularly regarding T-cell and macrophage-associated markers. Further investigation of these microenvironmental signatures may inform future diagnostic, prognostic, and therapeutic approaches in nonmelanoma skin cancers.
Reference
Winter L, Vogl C, Trumet L, et al. Comparative profiling of T cell and macrophage subsets in cutaneous squamous cell carcinoma and basal cell carcinoma. Sci Rep. 2025;15(1):35240. doi:10.1038/s41598-025-22486-1
