# Intraepithelial CD15 infiltration identifies high-grade anal dysplasia in people with HIV

## TL;DR

This study identifies CD15 infiltration as a marker for high-grade anal dysplasia in HIV-positive men who have sex with men, offering a potential diagnostic tool.

## Contribution

The study discovers CD15+ neutrophil infiltration as a novel biomarker for high-grade anal dysplasia in HIV-positive individuals.

## Key findings

- CD15+CD16+ mature neutrophils increase with the progression of anal lesions.
- CD15 staining in epithelium correlates with high-grade squamous intraepithelial lesions.
- Resident memory T cells and natural killer cell subsets show altered patterns in pathological samples.

## Abstract

Men who have sex with men (MSM) with HIV are at high risk for squamous intraepithelial lesion (SIL) and anal cancer. Identifying local immunological mechanisms involved in the development of anal dysplasia could aid treatment and diagnostics. Here, we studied 111 anal biopsies obtained from 101 MSM with HIV, who participated in an anal screening program. We first assessed multiple immune subsets by flow cytometry, in addition to histological examination, in a discovery cohort. Selected molecules were further evaluated by immunohistochemistry in a validation cohort. Pathological samples were characterized by the presence of resident memory T cells with low expression of CD103 and by changes in natural killer cell subsets, affecting residency and activation. Furthermore, potentially immunosuppressive subsets, including CD15+CD16+ mature neutrophils, gradually increased as the anal lesion progressed. Immunohistochemistry verified the association between the presence of CD15 in the epithelium and SIL diagnosis for the correlation with high-grade SIL. A complex immunological environment with imbalanced proportions of resident effectors and immune-suppressive subsets characterized pathological samples. Neutrophil infiltration, determined by CD15 staining, may represent a valuable pathological marker associated with the grade of dysplasia.

Assessment of changes in relevant anal dysplasia–associated mucosal immune subsets provides potential targets for immunotherapy and a complementary biomarker for current diagnostics.