MicroRNAs in Skin Cancers: Modulators of Immune Responses and Implications for Immunotherapy

Skin cancers, including melanoma and non-melanoma types such as basal cell carcinoma and cutaneous squamous cell carcinoma, represent a growing global health concern. Recent advances have highlighted the complex interplay between tumor cells and the immune microenvironment in driving cancer progression and therapy resistance. MicroRNAs (miRNAs), small non-coding RNA molecules that regulate gene expression post-transcriptionally, have emerged as critical modulators of immune responses in cancer. In skin tumors, miRNAs can influence immune evasion, inflammation, and immune cell infiltration, thereby shaping the tumor immune landscape. Understanding their role opens new avenues for biomarker discovery and the development of miRNA-targeted immunotherapies. This Research Topic aims to explore the regulatory functions of miRNAs in cutaneous malignancies, with a particular focus on their impact on antitumor immunity and the potential to enhance current immunotherapeutic strategies.

Despite significant progress in skin cancer immunotherapy, particularly with immune checkpoint inhibitors, many patients still experience suboptimal responses or resistance to treatment. One key factor contributing to this variability is the immunosuppressive tumor microenvironment, which can hinder effective antitumor immune responses. MicroRNAs (miRNAs) have been increasingly recognized as important regulators of this environment, modulating immune cell activation, cytokine production, antigen presentation, and the expression of immune checkpoints.

However, their exact role in skin cancers—especially in shaping immune evasion mechanisms—remains insufficiently understood. This Research Topic aims to address this knowledge gap by compiling studies that investigate the involvement of specific miRNAs in immune regulation within basal cell carcinoma, squamous cell carcinoma, and melanoma. Recent advances in miRNA profiling, in situ hybridization, and miRNA-based therapeutics now make it possible to precisely characterize their functions and therapeutic potential. By leveraging these technologies, researchers can identify novel miRNA targets to overcome resistance and enhance immunotherapy efficacy.

This Research Topic aims to explore the multifaceted roles of microRNAs in modulating immune responses in skin cancers and their implications for current and future immunotherapeutic strategies. We encourage submissions that contribute to understanding the interplay between non-coding RNA regulation and the tumor immune microenvironment in both non-melanoma and melanoma skin cancers.

We welcome the submission of Original Research, Review, Mini Review, and Perspective articles on themes including, but not limited to:

• Functional roles of specific microRNAs in immune modulation within cutaneous tumors

• MicroRNA-mediated regulation of immune checkpoint molecules (e.g., PD-1/PD-L1, CTLA-4)

• miRNAs involved in antigen presentation, T-cell infiltration, and immune escape mechanisms

• Diagnostic, prognostic, and predictive value of miRNA expression profiles in skin cancer

• Therapeutic potential of miRNA mimics or inhibitors to enhance immunotherapy

• Crosstalk between tumor cells, stromal cells, and immune cells via miRNA signaling