Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia.

Abstract:

:Chronic inflammation is now a well-known precursor for cancer development. Infectious prostatitis are the most common causes of prostate inflammation, but emerging evidence points the role of metabolic disorders as a potential source of cancer-related inflammation. Although the widely used treatment for prostate cancer based on androgen deprivation therapy (ADT) effectively decreases tumor size, it also causes profound alterations in immune tumor microenvironment within the prostate. Here, we demonstrate that prostates of a mouse model invalidated for nuclear receptors liver X receptors (LXRs), crucial lipid metabolism and inflammation integrators, respond in an unexpected way to androgen deprivation. Indeed, we observed profound alterations in immune cells composition, which was associated with chronic inflammation of the prostate. This was explained by the recruitment of phagocytosis-deficient macrophages leading to aberrant hyporesponse to castration. This phenotypic alteration was sufficient to allow prostatic neoplasia. Altogether, these data suggest that ADT and inflammation resulting from metabolic alterations interact to promote aberrant proliferation of epithelial prostate cells and development of neoplasia. This raises the question of the benefit of ADT for patients with metabolic disorders.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Bousset L,Septier A,Bunay J,Voisin A,Guiton R,Damon-Soubeyrant C,Renaud Y,De Haze A,Sapin V,Fogli A,Rambur A,De Joussineau C,Kocer A,Trousson A,Henry-Berger J,Höring M,Liebisch G,Matysik S,Lobaccaro JA,Morel L,Bar

doi

10.1371/journal.pbio.3000948

subject

Has Abstract

pub_date

2020-12-07 00:00:00

pages

e3000948

issue

12

eissn

1544-9173

issn

1545-7885

pii

PBIOLOGY-D-19-03570

journal_volume

18

pub_type

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