Introduction/Background Recurrent or residual cervical high-grade squamous intraepithelial lesions (rrcHSIL) occur in 5–27% of women after their first LLETZ and are often treated with another LLETZ, which further increases the risk of preterm birth in subsequent pregnancies. Imiquimod, a topical immunomodulator, is a non-invasive treatment alternative. However, effectivity of imiquimod in rrcHSIL is only 33%. A biomarker based on the pre-treatment immune infiltrate can predict response to imiquimod treatment in primary cHSIL. This study aimed to identify an immune profile predicting therapy responses to imiquimod in rrcHSIL. Furthermore, differences in the immune response between primary and rrcHSIL were studied.

Methodology Pre-imiquimod treatment rrcHSIL biopsies of 13 women underwent multispectral immunofluorescence staining to identify T cell and myeloid cell immune composition. Slides were scanned using Vectra multispectral imaging system and automatically phenotyped and counted using QuPath software.

Results The epithelium and stroma of rrcHSIL is infiltrated with a great amount of CD3+ T cells with only a limited subset expressing Tbet, high numbers of regulatory T cells and increased numbers of CD163+ myeloid cells. CD3+Tbet+/CD3+Tbet- ratios between primary and rrcHSIL are lower in rrcHSIL, indicating a lack of Th1 response. Additionally, there is a higher expression of CD14+HLADR- myeloid-derived suppressor cells (MDSCs) in non-responders to imiquimod in rrcHSIL compared to complete responders and primary cHSIL. In rrcHSIL with complete responses to imiquimod the immune microenvironment is comparable to primary cHSIL.

Conclusion The immune microenvironment of rrcHSIL is characterized by immunotolerance via Th2 immune infiltrates, which could explain the lower effectiveness of imiquimod in rrcHSIL.

Higher expression of MDSCs suggest a potential immunosuppressive environment in non-responders. Some rrcHSIL lesions do display immune infiltrates which may foster therapy responses to imiquimod application. This is crucial information for understanding the immune landscape in relation to therapy response and explore biomarkers to predict imiquimod efficacy.

Disclosures N/A