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Published on: March 6, 2018
Influence of Androgen Deprivation Therapy on the PD-L1 Expression and Immune Activity in Prostate Cancer Tissue
Ulrich Sommer1,2,3, Celina Ebersbach4,5, Alicia-Marie K Beier4,5
1Institute of Pathology, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
Abstract:
Immune checkpoint inhibitors have become a promising new therapy for cancer treatment. However, due to prostate cancer's high heterogeneity and immune-suppressive tumour microenvironment, clinical trials with immune checkpoint inhibitors for prostate cancer resulted in low or no response. This descriptive and retrospective study investigates the influence of androgen deprivation therapy (ADT) on PD-L1 expression and CD8+ T-cell tumour infiltration and activity in primary prostate cancer tissue. Therefore, immunohistochemistry was used to assess PD-L1, CD8+ T-cell, and the immune activation marker Granzyme B (GrB) in PCa tissue before and under ADT. In line with previous studies, few prostate cancer tissues showed PD-L1 expression and CD8+ T-cell infiltration. However, PD-L1 expression levels on tumour cells or infiltrating immune cells above 5% generated an immune-suppressive tumour microenvironment harbouring hypofunctional CD8+ T-cells. Moreover, analysis of a longitudinal patient cohort before and under ADT revealed that ADT increased hypofunctional CD8+ T cells in the tumour area suggesting a tumour immune milieu optimal for targeting with immunotherapy.
Insights
Androgen deprivation therapy may enhance prostate cancer immunotherapy. ADT increased hypofunctional CD8+ T cells, suggesting a more receptive tumor microenvironment for immune checkpoint inhibitors.
Area of Science:
- Oncology
- Immunology
Background:
- Immune checkpoint inhibitors (ICIs) show promise in cancer therapy but have limited efficacy in prostate cancer (PCa) due to tumor heterogeneity and immunosuppressive microenvironments.
- Prostate cancer's resistance to ICIs necessitates understanding factors influencing the tumor immune milieu.
Purpose of the Study:
- To investigate the impact of androgen deprivation therapy (ADT) on PD-L1 expression and CD8+ T-cell infiltration and activity in primary prostate cancer.
- To evaluate changes in the tumor immune microenvironment before and during ADT.
Main Methods:
- Retrospective descriptive study utilizing immunohistochemistry.
- Assessment of PD-L1, CD8+ T-cells, and Granzyme B (GrB) in prostate cancer tissues from patients before and under ADT.
Main Results:
- Limited PD-L1 expression and CD8+ T-cell infiltration were observed in most PCa tissues.
- PD-L1 expression above 5% correlated with an immunosuppressive tumor microenvironment and hypofunctional CD8+ T-cells.
- ADT treatment led to an increase in hypofunctional CD8+ T-cells within the tumor area.
Conclusions:
- ADT may create a tumor immune microenvironment more amenable to immunotherapy by increasing hypofunctional CD8+ T-cells.
- Further research is warranted to explore ADT in combination with immunotherapy for prostate cancer treatment.
