Objective:

To discuss the role of microRNAs (miRNAs) in the immune regulation of testicular germ cell tumors (TGCTs) and their potential as biomarkers and therapeutic targets in immunotherapy, particularly in light of the challenges faced in this area.

Approach:

Key Findings:

• TGCTs are the most common solid malignancies in young men, with a subset developing treatment-resistant disease.
• Immunotherapy has shown limited success in TGCT despite the presence of immune checkpoint molecules and tumor-infiltrating lymphocytes.
• MicroRNAs may influence the efficacy of immunotherapy in TGCT.

Interpretation:

The complexity of immune regulation in TGCT suggests that factors beyond PD-L1 expression influence treatment outcomes, necessitating further investigation into the role of miRNAs.

Limitations:

• Many proposed TGCT-associated miRNAs lack causal validation.
• The contribution of tumor mutational burden and microenvironmental factors to immune response remains unresolved.

Conclusion:

Future research should focus on mechanism-based, TGCT-specific strategies integrating miRNAs with immunotherapy to enhance treatment efficacy.

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