Localization of macrophage subtypes and neutrophils in the prostate tumor microenvironment and their association with prostate cancer racial disparities.

BACKGROUND: Black men are two to three times more likely to die from prostate cancer (PCa) than White men. This disparity is due in part to discrepancies in socioeconomic status and access to quality care. Studies also suggest that differences in the prevalence of innate immune cells and heightened function in the tumor microenvironment of Black men may promote PCa aggressiveness. METHODS: We evaluated the spatial localization of and quantified CD66ce+ neutrophils by immunohistochemistry and CD68+ (pan), CD80+ (M1), and CD163+ (M2) macrophages by RNA in situ hybridization on formalin-fixed paraffin-embedded tissues from organ donor "normal" prostate (n = 9) and radical prostatectomy (n = 38) tissues from Black and White men. Neutrophils were quantified in PCa and matched benign tissues in tissue microarray (TMA) sets comprised of 560 White and 371 Black men. Likewise, macrophages were quantified in TMA sets comprised of tissues from 60 White and 120 Black men. The phosphatase and tensin homolog (PTEN) and ETS transcription factor ERG (ERG) expression status of each TMA PCa case was assessed via immunohistochemistry. Finally, neutrophils and macrophage subsets were assessed in a TMA set comprised of distant metastatic PCa tissues collected at autopsy (n = 6) sampled across multiple sites. RESULTS: CD66ce+ neutrophils were minimal in normal prostates, but were increased in PCa compared to benign tissues, in low grade compared to higher grade PCa, in PCa tissues from White compared to Black men, and in PCa with PTEN loss or ERG positivity. CD163+ macrophages were the predominant macrophage subset in normal organ donor prostate tissues from both Black and White men and were significantly more abundant in organ donor compared to prostatectomy PCa tissues. CD68,+  CD80,+ and CD163+ macrophages were significantly increased in cancer compared to benign tissues and in cancers with ERG positivity. CD68+ and CD163+ macrophages were increased in higher grade cancers compared to low grade cancer and CD80 expression was significantly higher in benign prostatectomy tissues from Black compared to White men. CONCLUSIONS: Innate immune cell infiltration is increased in the prostate tumor microenvironment of both Black and White men, however the composition of innate immune cell infiltration may vary between races.

Effect of Donor Diet on In Vitro Digestibility of Forages by Fecal Inoculate.

Previous research indicates equine fecal inoculates produce comparable results to cecal fluid when used for in vitro procedures to analyze dry matter digestibility (DMD). Equine hindgut microbial communities represented in fecal samples have been shown to be affected by diet. The study's objective was to determine the effect of the donor diet on in vitro DMD when fecal donors were fed high starch, or high fiber diets. Six Quarter Horses were used in a crossover design to compare the effects of a grain versus forage diet on in vitro digestion of forages ranging from: CP 7.7 to 16.4 %DM, NDF 53 to 72 %DM. Feces from each horse were obtained on day 22 of each period and used to inoculate in vitro fermentation vessels in order to evaluate the effect of donor diet on the DMD, neutral detergent fiber digestibility (NDFD), and acid detergent fiber digestibility (ADFD) of four forages. Data were analyzed using the MIXED procedure of SAS to evaluate digestibility differences in the diet by forage composition interaction. Fecal samples from horses on the grain diet promoted higher NDFD of forages with high NDF and low CP when CP and NDF were used as covariates (P = .04 and .03). There was a horse effect on DMD and NDFD (P ≤ .05). Findings suggest diet may influence the hindgut microbiome's ability to digest neutral detergent fiber and should be considered when selecting equine fecal samples for in vitro digestion procedures.