Arginine availability and activation of arginine-related pathways at cancer sites have profound effects on the tumor microenvironment, far beyond their well-known role in the hepatic urea cycle. Arginine metabolism impacts not only malignant cells but also the surrounding immune cells behavior, modulating growth, survival, and immunosurveillance mechanisms, either through an arginase-mediated effect on polyamines and proline synthesis, or by the arginine/nitric oxide pathway in tumor cells, antitumor T-cells, myeloid-derived suppressor cells, and macrophages. This review presents evidence concerning the impact of arginine metabolism and arginase activity in the prostate cancer microenvironment, highlighting the recent advances in immunotherapy, which might be relevant for prostate cancer. Even though further research is required, arginine deprivation may represent a novel antimetabolite strategy for the treatment of arginine-dependent prostate cancer.

To assess body composition, nutritional status and its differences between genders in a sample of Portuguese centenarians.

Periprostatic adipose tissue (PPAT) has been recognized to associate with prostate cancer (PCa) aggressiveness and progression. Here, we sought to investigate whether excess adiposity modulates the methylome of PPAT in PCa patients. DNA methylation profiling was performed in PPAT from obese/overweight (OB/OW, BMI > 25 kg m−2) and normal weight (NW, BMI < 25 kg m−2) PCa patients. Significant differences in methylated CpGs between OB/OW and NW groups were inferred by statistical modeling. Five thousand five hundred twenty-six differentially methylated CpGs were identified between OB/OW and NW PCa patients with 90.2% hypermethylated. Four hundred eighty-three of these CpGs were found to be located at both promoters and CpG islands, whereas the representing 412 genes were found to be involved in pluripotency of stem cells, fatty acid metabolism, and many other biological processes; 14 of these genes, particularly FADS1, MOGAT1, and PCYT2, with promoter hypermethylation presented with significantly decreased gene expression in matched samples. Additionally, 38 genes were correlated with antigen processing and presentation of endogenous antigen via MHC class I, which might result in fatty acid accumulation in PPAT and tumor immune evasion. Results showed that the whole epigenome methylation profiles of PPAT were significantly different in OB/OW compared to normal weight PCa patients. The epigenetic variation associated with excess adiposity likely resulted in altered lipid metabolism and immune dysregulation, contributing towards unfavorable PCa microenvironment, thus warranting further validation studies in larger samples.