Background Prostate cancer (PCa) is one of the most frequently diagnosed cancers in the world. Emerging evidence suggests that inflammatory cells such as M2 macrophages and regulatory T cells (T regs ) can contribute to cancer progression by suppressing the anti‐tumor immune response. This study investigated the number of CD163‐positive M2 macrophages in PCa tissue. It also investigated the correlation and interaction of M2 macrophages and T regs . Methods This nested case‐control study included subjects from a cohort of men diagnosed with PCa as an incidental finding during transurethral resection of the prostate. The cases were 225 men who died from PCa, and the controls were 367 men who survived more than 10 years after PCa diagnosis without disease progression. Infiltrating CD163‐positive M2 macrophages and FOXP3/CD4‐positive T regs in PCa tissue were identified using immunohistochemistry. The correlation and interaction of M2 macrophages and T regs were assessed using Spearman's rank‐order correlation and a likelihood test, respectively. Logistic regression was used to estimate odds ratios (ORs) for lethal PCa and macrophage counts. Results The number of M2 macrophages and T regs showed a significant correlation ( P < 0.001) but no interactions. The OR for lethal PCa was 1.93 (95%CI: 1.23‐3.03) for men with high numbers of M2 macrophages. Also for cases with uncertain outcome (GS categories 3 + 4 and 4 + 3) high numbers of M2 macrophages does predict a poorer prognosis. Conclusions Our data showed that men with high numbers of M2 macrophages in the prostate tumor environment had increased odds of dying of PCa. It is possible that M2 macrophages, together with other suppressor cells such as T regs , promote an immunosuppressive environment.
Prostate cancer represents a major contributor to cancer mortality, but the majority of men with prostate cancer will die of other causes. Thus, a challenge is identifying potentially lethal disease at diagnosis. Conflicting results have been reported when investigating the relationship between infiltration of lymphocytes and survival in prostate cancer. One of the mechanisms suggested is the recruitment of regulatory T cells (T regs ), a subpopulation of T cells that have a role in promoting tumor growth. T regs counteract tumor rejection through suppressive functions on the anti-immune response but their prognostic significance is still unknown. We report here the results of a conducted case-control study nested in a cohort of men treated with transurethral resection of the prostate and diagnosed incidentally with prostate cancer. Cases are men who died of prostate cancer (n ¼ 261) and controls are men who survived 410 years after their diagnosis (n ¼ 474). Infiltration of both T helper and T cytotoxic cells was frequently observed and the majority of the T regs were CD4 þ . T helper or T cytotoxic cells were not associated with lethal prostate cancer. However, we found a nearly twofold increased risk of lethal prostate cancer when comparing the highest with the lowest quartile of CD4 þ T reg cells (95% confidence interval: 1.3-2.9). Our conclusion is that men with greater numbers of CD4 þ T regs in their prostate tumor environment have an increased risk of dying of prostate cancer. Identification of CD4 þ T regs in tumor tissue may predict clinically relevant disease at time of diagnosis independently of other clinical factors.
Background A challenge in prostate cancer (PCa) management is identifying potentially lethal disease at diagnosis. Inflammation, focal prostatic atrophy and prostatic intraepithelial neoplasia (PIN) are common in prostate tumor specimens, but it is not clear whether these lesions have prognostic significance. Methods We conducted a case-control study nested in a cohort of men diagnosed with stage T1a-b PCa through transurethral resection of the prostate in Sweden. Cases are men who died of PCa (n=228). Controls are men who survived more than 10 years after PCa diagnosis without metastases (n=387). Slides were assessed for Gleason grade, inflammation, PIN, and four subtypes of focal prostatic atrophy: simple atrophy (SA), post-atrophic hyperplasia (PAH), simple atrophy with cyst formation, and partial atrophy. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for odds of lethal PCa with multivariable logistic regression. Results Chronic inflammation and PIN were more frequently observed in tumors with PAH, but not SA. No specific type of atrophy or inflammation was significantly associated with lethal PCa overall, but there was a suggestion of a positive association for chronic inflammation. Independent of age, Gleason score, year of diagnosis, inflammation, and atrophy type, men with PIN were 89% more likely to die of PCa (95% CI:1.04-3.42). Conclusions Our data demonstrate that PIN, and perhaps presence of moderate or severe chronic inflammation, may have prognostic significance for PCa. Impact Lesions in tumor adjacent tissue, and not just the tumor itself, may aid in identification of clinically relevant disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.