# TMPRSS2 Expression in Lung Tissue of Prostatic Adenocarcinoma Patients: Androgen Deprivation Therapy and Relevance to SARS-CoV-2 Infection

## TL;DR

This study shows that prostate cancer treatments that lower androgen levels also reduce a protein in the lungs that helps SARS-CoV-2 enter cells, possibly explaining why some men are less likely to get severe COVID-19.

## Contribution

The study demonstrates that androgen deprivation therapy reduces pulmonary TMPRSS2 expression, with direct AR antagonists being most effective.

## Key findings

- ADT significantly lowers lung TMPRSS2 expression in prostate cancer patients.
- Direct AR antagonists suppress TMPRSS2 more than other ADT regimens.
- Reduced TMPRSS2 may explain lower SARS-CoV-2 infection severity in treated patients.

## Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry is facilitated by transmembrane protease serine 2 (TMPRSS2), which is regulated by the androgen receptor (AR). Androgen deprivation therapy (ADT), widely used in prostate cancer treatment, may potentially modulate TMPRSS2 expression, affecting SARS-CoV-2 infection susceptibility and severity. We evaluated the impact of ADT on pulmonary TMPRSS2 expression in prostate cancer patients and analyzed differences in expression patterns associated with specific ADT regimens. We examined TMPRSS2 immunohistochemical expression in lung tissue from 20 consecutive autopsy cases of men with prostate cancer (6 receiving ADT at time of death), compared with non-ADT prostate cancer patients and age-matched women controls. Histoscores were calculated by assessing the percentage and intensity of pneumocyte TMPRSS2 expression. Prostate cancer patients receiving ADT showed significantly reduced pulmonary TMPRSS2 expression compared to non-ADT patients (mean histoscores: 152.7 vs. 225.0, p = 0.037) and age-matched women controls (mean histoscores: 152.7 vs. 238.0, p = 0.024). Direct AR antagonists (apalutamide, bicalutamide) produced greater TMPRSS2 suppression than Gonadotropin-Releasing Hormone modulators or androgen biosynthesis inhibitors. No significant correlation was observed between the TMPRSS2 expression and Gleason score, PSA levels, or underlying lung pathology. Our findings demonstrate that ADT significantly reduces pulmonary TMPRSS2 expression, with direct AR antagonists showing the strongest effect. This suggests a potential mechanistic explanation for differential COVID-19 susceptibility and provides a rationale for investigating AR-targeted therapies as potential protective interventions against SARS-CoV-2 infection severity.