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47 A pre-existing coordinated immune response is pivotal to treatment response to imiquimod in primary and recurrent vulvar high-grade squamous intraepithelial lesions
  1. Caroline LP Muntinga1,2,
  2. Peggy J De Vos Van Steenwijk2,3,
  3. Ziena Abdulrahman4,
  4. Ruud LM Bekkers1,2,
  5. Sjoerd HVan Der Burg4,
  6. Gerda Trutnovsky5 and
  7. Edith MGVan Esch1
  1. 1Catharina Hospital, Eindhoven, The Netherlands
  2. 2Maastricht University: GROW – School for Oncology and Reproduction, Maastricht, The Netherlands
  3. 3Maastricht University Medical Centre, Maastricht, The Netherlands
  4. 4Leiden University Medical Centre, Leiden, The Netherlands
  5. 5Medical University of Graz, Graz, Austria


Introduction/Background Imiquimod is a safe and effective topical immunotherapy as a non-invasive alternative to surgery for treatment of vulvar high-grade squamous intraepithelial lesions (vHSIL), with complete response rates up to 80%. Research shows response to imiquimod therapy in primary vHSIL is related to a pre-existing coordinated immune response. Moreover, in cervical HSIL a biomarker based on the pre-treatment immune infiltrate can predict response to imiquimod treatment. This study aimed to identify an immune profile predicting therapy responses to imiquimod in vHSIL. Furthermore, an in-depth analysis of the tumor microenvironment was performed to evaluate the immunologic differences between primary and recurrent vHSIL regarding therapy responses to imiquimod.

Methodology Pre-imiquimod treatment vHSIL biopsies of 38 patients included in the PITVIN trial 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 immune microenvironment of complete responders to imiquimod show a coordinated influx of CD14+ inflammatory myeloid cells and type 1 CD4+ and CD3+CD8+ T cells, both in and between epithelial and stromal compartments. The persistent lesions did not display such a coordinated immune response. Importantly, recurrent vHSIL are able to respond to imiquimod in a comparable manner to primary vHSIL when a pre-existent coordinated immune infiltrate is present.

Conclusion A coordinated influx of type 1 T cells and myeloid cells is pivotal in achieving a complete response to imiquimod in vHSIL, irrespective of primary or recurrent vHSIL. Topical imiquimod therapy enhances the pre-existing pro-inflammatory immune infiltrates to induce lesion regression, however if the pre-existing immune microenvironment does not exhibit this coordinated influx of pro-inflammatory cells lesion regression is less probable. Currently, predictive biomarkers are analysed to personalize patient selection for imiquimod and other therapeutic options, and to improve patient outcomes in vHSIL management.

Disclosures N/A

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