Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia - Université Clermont Auvergne Accéder directement au contenu
Article Dans Une Revue PLoS Biology Année : 2020

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

Yoan Renaud
Vincent Sapin
Gerhard Liebisch
Silvère Baron

Résumé

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.

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Cancer Immunologie
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Origine : Publication financée par une institution

Dates et versions

hal-03252478 , version 1 (07-06-2021)

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Laura Bousset, Amandine Septier, Julien Bunay, Allison Voisin, Rachel Guiton, et al.. Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia. PLoS Biology, 2020, 18 (12), pp.e3000948. ⟨10.1371/journal.pbio.3000948⟩. ⟨hal-03252478⟩
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