Influence of Androgen Deprivation Therapy on the PD-L1 Expression and Immune Activity in Prostate Cancer Tissue

Ulrich Sommer; Celina Ebersbach; Alicia-Marie K Beier; Gustavo B Baretton; Christian Thomas; Angelika Borkowetz; Holger H H Erb

doi:10.3389/fmolb.2022.878353

Influence of Androgen Deprivation Therapy on the PD-L1 Expression and Immune Activity in Prostate Cancer Tissue

Front Mol Biosci. 2022 Jun 28:9:878353. doi: 10.3389/fmolb.2022.878353. eCollection 2022.

Authors

Ulrich Sommer^{1

2

3}, Celina Ebersbach^{4

5}, Alicia-Marie K Beier^{4

5}, Gustavo B Baretton^{1

2

3}, Christian Thomas^{2

4}, Angelika Borkowetz⁴, Holger H H Erb⁴

Affiliations

¹ Institute of Pathology, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany.
² National Center for Tumor Diseases Partner Site Dresden and German Cancer Center Heidelberg, Dresden, Germany.
³ Tumor and Normal Tissue Bank of the University Cancer Center (UCC), University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
⁴ Department of Urology, Technische Universität Dresden, Dresden, Germany.
⁵ Department of Urology, Mildred Scheel Early Career Center, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität 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.

Keywords: ADT; PCA; checkpoint inhibitors; immune therapy; tumour microenvironment (TME).