Infiltrating immune cells in prostate cancer tissue after androgen deprivation and radiotherapy

Author:

Erlandsson Ann12ORCID,Lundholm Marie3,Watz Johan2,Bergh Anders3,Petrova Elitsa4,Alamdari Farhood5,Helleday Thomas6,Davidsson Sabina1,Andren Ove1,Tarish Firas6

Affiliation:

1. Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden

2. Department of Environmental and Life Sciences/Biology, Karlstad University, Karlstad, Sweden

3. Department of Medical Biosciences, Umeå University, Umeå, Sweden

4. Department of Clinical Pathology and Cytology, Central Hospital Karlstad, Karlstad, Sweden

5. Department of Urology, Västmanlands Hospital, Västerås, Sweden

6. Department of Oncology-Pathology, Karolinska Institutet, Science for Life Laboratory, Stockholm, Sweden

Abstract

Objectives Androgen deprivation therapy (ADT) has long been a cornerstone in treatment of advanced prostate cancer (PCa), and is known to improve the results of radiotherapy (RT) for high-risk disease. The purpose of our study was to use a multiplexed immunohistochemical (mIHC) approach to investigate the infiltration of immune cells in PCa tissue after eight weeks of ADT and/or RT with 10 Gy. Methods From a cohort of 48 patients divided into two treatment arms, we obtained biopsies before and after treatment and used a mIHC method with multispectral imaging to analyze the infiltration of immune cells in tumor stroma and tumor epithelium, focusing on areas with high infiltration. Results Tumor stroma showed a significantly higher infiltration of immune cells compared to tumor epithelium. The most prominent immune cells were CD20+ B-lymphocytes, followed by CD68+ macrophages, CD8+ cytotoxic T-cells, FOXP3+ regulatory T-cells (Tregs), and T-bet+ Th1-cells. Neoadjuvant ADT followed by RT significantly increased the infiltration of all five immune cells. Numbers of Th1-cells and Tregs significantly increased after single treatment with ADT or RT. In addition, ADT alone increased the number of cytotoxic T-cells and RT increased the number of B-cells. Conclusions Neoadjuvant ADT in combination with RT results in a higher inflammatory response compared to RT or ADT alone. The mIHC method may be a useful tool for investigating infiltrating immune cells in PCa biopsies to understand how immunotherapeutic approaches can be combined with current PCa therapies.

Funder

Research Collaboration Region Värmland and Karlstad University

Regional Research Council Mid Sweden

Publisher

SAGE Publications

Subject

Pharmacology,Immunology,Immunology and Allergy,Pharmacology,Immunology,Immunology and Allergy

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