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[MHC-class I expression on prostate carcinoma and modulation by IFN-gamma]
Michio Naoe1, Yoshiko Marumoto, Keiichiro Aoki
1Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA, Department of Urology, Showa University, School of Medicine, Tokyo, Japan.
Insights
Prostate cancer exhibits reduced MHC-class I expression, correlating with fewer CD8+ T cells. Interferon-gamma (IFN-gamma) boosts MHC-class I expression, potentially enhancing tumor immunity.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Context:
- Prostate cancer is characterized by altered immune cell infiltration and antigen presentation.
- MHC-class I expression is crucial for cytotoxic T lymphocyte (CTL) recognition of tumor cells.
- Reduced tumor-infiltrating lymphocytes (TILs) are associated with poor prognosis in prostate cancer.
Purpose:
- To investigate the correlation between MHC-class I expression and CD8+ T cell infiltration in prostate cancer.
- To evaluate the effect of Interferon-gamma (IFN-gamma) on MHC-class I expression in prostate carcinoma.
Summary:
- Immunohistochemistry revealed a significant positive correlation between MHC-class I expression and CD8+ T lymphocyte infiltration in prostate cancer tissues (r = 0.705, P < 0.0001).
- Flow cytometry analysis demonstrated that IFN-gamma stimulation up-regulates MHC-class I expression on prostate carcinoma cells (p < 0.05).
Impact:
- Findings suggest that diminished MHC-class I expression may contribute to reduced TILs in prostate cancer.
- IFN-gamma, potentially secreted by CTLs, could enhance anti-tumor immunity by increasing MHC-class I expression and TILs.
Objectives:
In this study, we investigated MHC-class I expression on both prostate cancer and normal prostate and compared those data with the number of CD8+ lymphocyte. Secondary, we investigated effect of IFN-gamma to the MHC-class I expression on prostate carcinoma.
Materials And Methods:
Twenty cryo-preserved benign prostate samples (Seven normal prostates and five benign prostatic hypertrophy samples.) and fifteen prostate carcinoma samples were used for immunohistochemistry of CD8 and MHC-class I. Eleven fresh single cell suspensions of prostate carcinoma were used for IFN-gamma study. After 24 hours IFN-gamma stimulation, MHC-I expression was measured by FACs analysis.
Results:
Interestingly, significant correlation was observed between MHC-class I expression and the CD8+ lymphocyte infiltrate (r = 0.705, P < 0.0001). After 24 hrs IFN-gamma stimulation, MHC-class I expression was up-regulated in all samples (p < 0.05).
Conclusion:
Reduced expression of MHC-class I was thought as one of the factor which is related to the reduced degree of TILs (tumor infiltratig lymphocytes) in prostate cancer. IFN-gamma which is secreted mainly from CTL (cytotoxic T lymphocyte) might increase the degree of TIL through up-regulated MHC-class I.