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Exploring the Complexity of Cutaneous Squamous CellCarcinoma Microenvironment: Focus on Immune Cell Roles by Novel 3D
Marika Quadri1, Marco Iuliano2, Paolo Rosa2,3
1DermoLab, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
Life (Basel, Switzerland)
|August 28, 2025
Summary
Cutaneous squamous cell carcinoma (cSCC) progression involves complex tumor microenvironment (TME) interactions. Advanced 3D models offer new ways to study immune responses and develop better immunotherapies for skin cancer.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Non-melanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), is the most common cancer globally.
- cSCC is an aggressive cancer with high metastatic potential, influenced by the tumor microenvironment (TME).
- Immune cells like T cells, macrophages (TAMs), and dendritic cells play crucial roles in cSCC progression, immune evasion, and treatment resistance.
Purpose of the Study:
- To review regulatory mechanisms within the cSCC immune TME.
- To explore the roles of cytokines, immune checkpoints, and stromal interactions in cSCC.
- To discuss the utility of 3D in vitro models for studying immune-tumor interactions in cSCC.
Main Methods:
- Literature review of immune TME regulatory mechanisms in cSCC.
- Analysis of the roles of cytokines, immune checkpoints, and stromal interactions.
- Evaluation of 3D in vitro models (spheroids, organoids, tumor-on-chip) for mimicking cSCC immune-tumor dynamics.
Main Results:
- The immune TME significantly impacts cSCC development, progression, and metastasis.
- 3D models provide higher physiological relevance for studying immune cell functions like macrophage activation against cSCC.
- These models facilitate immunotherapy screening and mechanistic investigations.
Conclusions:
- Understanding the cSCC immune landscape is critical for advancing diagnostic and therapeutic strategies.
- Advanced 3D models are valuable tools for dissecting complex immune-tumor interactions.
- Further research using these models holds significant clinical potential for improving cSCC treatment.

