Impaired access of lymphocytes to neoplastic prostate tissue is associated with neoangiogenesis in the tumour site

Abstract

Recent reports demonstrated that neovasculature of certain murine tumours inhibits migration of lymphocytes to malignant tissues. We examined the possible existence of this phenomenon in human prostate adenocarcinoma by relating extent, patterns and composition of leucocyte infiltrates in adenocarinoma specimens (N ¼ 28) to microvessel density and percentages of these vessels expressing adhesion molecules CD54, CD106 and CD62E. Specimens of nodular hyperplasia (N ¼ 30) were used as a control for nonmalignant prostate. Increased microvessel density was detected in foci of adenocarcinoma, as compared with adjacent benign areas (P ¼ 0.004) or hyperplastic specimens (P ¼ 0.001). Only CD54 was detected on prostate vasculature; percentages of CD54-expressing vessels in adenocarcinoma lesions and adjacent areas were higher than in hyperplasia (P ¼ 0.041 and P ¼ 0.014, respectively). Infiltrating leucocytes were either scattered diffusely in tissue or organised into clusters mainly composed of CD4-positive lymphocytes; smaller percentage of tissue was occupied by clustered infiltrates in adenocarcinoma foci (mean ¼ 0.7; median ¼ 0; range ¼ 0 -5) than in adjacent tissue (mean ¼ 2.5; median ¼ 1; range ¼ 0 -15; P ¼ .021) and hyperplasia (mean ¼ 1.9; median ¼ 2; range ¼ 0-5; P ¼ .006). In adenocarcinoma foci, microvessel density tended to negatively correlate with percentage of tissue occupied by an overall leucocyte infiltrate (mean ¼ 8.6; median ¼ 7.5; range ¼ 30) and negatively correlated with percentage of tissue occupied by clustered infiltrate (P ¼ 0.045). Percentage of CD54-expressing vessels positively correlated with percentage of tissue occupied by an overall (mean ¼ 12; median ¼ 10; range ¼ 30; P ¼ 0.01) and clustered (P ¼ 0.023) infiltrate in hyperplasia, whereas in carcinoma-adjacent benign areas, correlation was detected only for clustered infiltrates (P ¼ 0.02). The results indicate that impaired access of lymphocytes to malignant lesions is associated with increased numbers of newly formed blood vessels, whereas vascular CD54 likely contributes to extravasation of lymphocytes only in benign prostate tissue.

Prostate inflammation and its potential impact on prostate cancer: A current review

“…Indeed a barrier function for tumor vasculature has been suggested due to decreased levels of adhesion molecules on endothelial cells in both breast and renal cell carcinomas. This finding was extended to prostate tumor neovasculature by demonstrating impaired extravasation of lymphocytes into prostate tumors due to loss of adhesion molecules on tumor blood vessels [Fedida et al, 2007]. The concept that the tumor vasculature acts as a barrier to infiltrating lymphocytes is in apparent contradiction with data from McArdle et al 2004 who demonstrated that prostate tumors had elevated numbers of CD4 and CD8 T cells.…”