9. Cellular immune response to anal dysplasia in HIV-positive men on highly active antiretroviral therapy

Abstract

Background: The role of the cellular immune response to anal dysplasia progression is poorly understood. Extrapolated from the cervical model, CD4+ (killed by HIV) and CD8+ cells may have crucial anti-tumour activity. We report pilot data on key immune responses in HIV+ patients on HAART with anal dysplasia. Methods: High-resolution anoscopy and biopsies were performed. Ten tissue biopsies with high-grade anal intraepithelial neoplasia (HGAIN) were stained with immunohistochemistry for CD4+, CD8+, CXCL12+ and FOXP3+, and compared with 10 samples with low-grade anal intraepithelial neoplasia (LGAIN). Serum CD4+ and CD8+ counts were available. Tissue photographs were obtained and analysed utilising MetaXpress software. Results: In all dysplastic tissue, we found a higher number of CD4+, CD8+ and FOXP3+ cells in the subepithelium than epithelium. In HGAIN, the number of FOXP3+, intraepithelial CD4+ cells, and the ratio of intraepithelial to serum CD4+ were higher than in LGAIN. CXCL12+ staining was more abundant in HGAIN. CD4+ cells outnumbered CD8+ cells in all dysplastic tissue. Conclusions: The higher CD4+ to CD8+ ratio in HGAIN may be explained by the excess demand for antitumour activity, which is known to be a function of CD4+ cells against HPV-dysplasia in the analogous cervical dysplasia model. Cytotoxic CD8 cells, although known to have an important anti-tumour role, were less abundant in our study. The pro-tumour FOXP3+ cells, being more abundant in HGAIN, may have a key role in the progression of anal dysplasia. Strategies to block CXCL12+ may be useful in the treatment of HPV-related dysplasia.