IL-38 promotes the development of prostate cancer

Front Immunol. 2024 May 8:15:1384416. doi: 10.3389/fimmu.2024.1384416. eCollection 2024.

Abstract

Introduction: Prostate Cancer (PCa) remains a significant concern in male cancer-related mortality. Tumour development is intricately regulated by the complex interactions between tumour cells and their microenvironment, making it essential to determine which is/are key factor(s) that influence the progression of PCa within the tumour microenvironment.

Materials and methods: The current study utilised histopathology and immunohistochemistry to determine the expression of IL-38 in PCa and analysed the correlation between the expression level of IL-38 within PCa and clinical pathological characteristics.

Results: There was a significant increase in IL-38 expression in PCa tissues compared to adjacent non-PCa tissues (P < 0.0001). In addition, IL-38 expression was significantly higher in tumour cells with a high proliferation index compared to those with a low value-added index. ROC curve analysis demonstrated that IL-38 has high specificity and sensitivity for the diagnosis of PCa (AUC=0.76). Moreover, we Probed the cellular source of IL-38 in prostate cancer tissue by immunofluorescence double staining. Additionally, within PCa, the expression of IL-38 was inversely correlated with the expression levels of CD8 and PD-1. Survival analysis revealed a significantly lower overall survival rate for PCa patients with high IL-38 expression (P=0.0069), and when IL-38 was co-expressed with CD8, the survival rate of the IL-38high/CD8low group was decreased significantly. Multivariate analysis indicated that the expression level of IL-38 and TNM staging were independent predictors of survival in PCa patients.

Conclusion: These findings suggest that IL-38 plays a crucial role in the development of PCa, and the exploration of the correlation between IL-38 and various immune factors in the tumour microenvironment further reveals its mechanism of action, making it a potential target for immunotherapy in PCa.

Keywords: CD4; CD8; IL-38; PD-1; prognosis; prostate cancer.

MeSH terms

  • Aged
  • Biomarkers, Tumor
  • Humans
  • Interleukins* / metabolism
  • Male
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism
  • Prostatic Neoplasms* / immunology
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / mortality
  • Prostatic Neoplasms* / pathology
  • Tumor Microenvironment / immunology

Substances

  • Biomarkers, Tumor
  • IL-38 protein, human
  • Interleukins
  • Programmed Cell Death 1 Receptor

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded by Shanghai Hospital Development Center Foundation (SHDC22023209).