Distinct tumor microenvironment profiles characterize regressive versus progressive anal precancers.

Authors

Fernando Dias Goncalves Lima, Marieke E Ijsselsteijn, Johanna F Verkerk, Kirsten Rozemeijer, Carel J M van Noesel, Noel F C C de Miranda, Jan M Prins, Rosalie M Luiten, Renske D M Steenbergen, Henry J C de Vries

Published in

iScience. Volume 29. Issue 10. Pages 117404. Oct 16, 2026. Epub Sep 21, 2026.

Abstract

Oncogenesis of anal high-grade squamous intraepithelial lesions (HSIL) is highly variable. Therefore, all HSIL are ablated, leading to overtreatment and associated burden because not all lesions will progress to cancer. This exploratory study investigated differences in the tumor immune microenvironment between regressive and progressive HSIL in people living with HIV to enable a more tailored approach. Multiplex imaging mass cytometry showed more inflammation in HSIL that progressed to cancer and cancer samples, compared with HSIL that spontaneously regressed and controls. Densities of HLA-DR⁺ macrophage phenotypes were higher in regressive HSIL, while progressive HSIL showed a predominance of CD163⁺ and/or CD204⁺, HLA-DR^- macrophage phenotypes. Validation with immunofluorescence confirmed this phenotypical distribution. Moreover, HSIL lesions closest to progression, and HSIL in individuals with a low nadir CD4 count, showed more unfavorable macrophage profiles. These preliminary findings may support the development of biomarkers or immunotherapeutic targets, enabling more individualized treatment approaches for anal HSIL.

PMID:
42820243
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

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