HLA Class I Expression Is Associated with Increased Immune Cell Density and PTEN Loss in Prostate Cancer

Area of Science:

• Oncology
• Immunology
• Genetics

Background:

• Prostate cancer progression involves immune evasion, potentially linked to Human Leukocyte Antigen Class I (HLA-I) downregulation.
• Understanding HLA-I expression dynamics is crucial for developing effective cancer immunotherapies.

Purpose of the Study:

• To quantify HLA-I protein expression across various prostate cancer stages (primary, metastatic hormone-sensitive, castration-resistant).
• To investigate associations between HLA-I expression, tumor methylation, race, clinicopathologic features, and PTEN status.
• To explore the relationship between HLA-I expression and immune cell infiltration.

Main Methods:

• Digital quantification of HLA-I protein expression in prostatectomy specimens and metastatic cohorts.
• Analysis of HLA-I gene methylation, race, genetic ancestry, and clinicopathologic parameters.
• Validation in pre-clinical cell line and animal models.

Main Results:

• HLA-I expression is downregulated in tumors versus benign glands and negatively associated with HLA-I gene methylation.
• HLA-I expression is higher in metastatic hormone-sensitive prostate cancer (mHSPC) lymph node metastases.
• Primary tumor HLA-I expression correlates positively with immune cell densities and surprisingly higher in tumors with PTEN loss.

Conclusions:

• Prostate cancer exhibits complex HLA-I expression patterns influenced by methylation and metastatic status.
• PTEN loss is a novel correlate of increased tumoral HLA-I expression, potentially enhancing immune cell infiltration.
• These findings may inform precision medicine approaches for prostate cancer treatment.