Crosstalk Between COVID-19 and Prostate Cancer

Promising data have come out recently that points to a possible link between prostate cancer and COVID-19, where androgen-deprivation therapies used in prostate cancer have been shown to instigate a protective role against COVID-19. This is due to the crosstalk between COVID-19 and prostate cancer at the level of genetic aberrations and molecular signatures that are common between the two diseases, including AR and TMPRSS2. It is still not clear, however, whether higher expression of ACE2/TMPRSS2 is related to high viral load in the tissues, at least within the lung, for COVID-19 patients. The first/major line of exposure/defense against pathogens like SARS-CoV-2 are mucosal epithelial barriers in the host (e.g. respiratory, intestinal). Unfortunately, strategies to limit infection of these barriers by SARS-CoV-2 are proving to be contentious because there are multiple routes and mechanisms of entry.

Upon viral infection, the initial step for clearing the virus depends on the successful recognition of infected cells by the immune system, which depends on cell surface receptor interactions, followed by the subsequent immune response. Given that viruses alter protein synthesis and thus affect cell surface receptors, the immune response encounters several barriers such as decreased recognition by immune cells and ineffective cytotoxicity by the exhaustion of T cells. Therefore, a holistic therapeutic approach that relies on targeting the viral infection at two levels might be worth considering: the first includes altering mucosal epithelial barriers and preventing viral entry to host cells (via targeting TMPRSS2 for instance) and the second encompasses immune-based treatment (e.g. interferon treatments emulating/stimulating anti-viral responses or anti-inflammatory agents) that are likely to and even proving to be valuable.

Interestingly, the prostate differs from other organs in our body by being immune privileged; it is not mucosal like the lung or colon tissues. That is since the prostate is immune-privileged (not a site of innate immune responses), it is possible that androgen-deprivation therapy could serve as adjunctive therapy with immune-based therapies to reduce risk of SARS-CoV-2 infection in prostate cancer patients specifically, and COVID-19 patients in general, independent of local mechanisms in the prostate itself.

Written by: Hisham F. Bahmad and Wassim Abou-Kheir, Department of Anatomy, Cell Biology, and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut

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