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A pre-existing coordinated inflammatory microenvironment is associated with complete response of vulvar high-grade squamous intraepithelial lesions to different forms of immunotherapy.
- Source :
-
International journal of cancer [Int J Cancer] 2020 Nov 15; Vol. 147 (10), pp. 2914-2923. Date of Electronic Publication: 2020 Jul 03. - Publication Year :
- 2020
-
Abstract
- Immunotherapy of vulvar high-grade squamous intraepithelial lesion (vHSIL) is investigated as an alternative for surgery, because of high comorbidity and risk of recurrence. Limited evidence exists on the role and composition of the immune microenvironment in current immunotherapeutic approaches for vHSIL. The vHSIL of 29 patients biopsied before treatment with imiquimod were analyzed by two multiplex seven-color immunofluorescence panels to investigate the pre-existing T-cell and myeloid cell composition in relation to treatment response. The samples were scanned with the Vectra multispectral imaging system. Cells were automatically phenotyped and counted with inForm advanced image analysis software. Cell counts and composition were compared to that of vHSIL patients before therapeutic vaccination (n = 29) and to healthy vulva (n = 27). Our data show that the immune microenvironment of complete responders (CR) to imiquimod resembled the coordinated infiltration with type 1 CD4 <superscript>+</superscript> and CD8 <superscript>+</superscript> T cells and CD14 <superscript>+</superscript> inflammatory myeloid cells also found in healthy vulva. However, more CD8 <superscript>+</superscript> T cells and FoxP3 <superscript>+</superscript> regulatory T cells were present in CR. The lesions of partial responders (PR) lacked such a coordinated response and displayed an impaired influx of CD14 <superscript>+</superscript> inflammatory myeloid cells. Importantly, complete responses after imiquimod or therapeutic vaccination showed the same dependency on a pre-existing coordinated type 1 T-cell and CD14 <superscript>+</superscript> myeloid cell infiltration. In conclusion, a good clinical outcome after two different forms of immunotherapy for vHSIL is associated with the presence of a primary inflammatory process resulting in the coordinated influx of several types of immune cells which is then amplified.<br /> (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
- Subjects :
- Adjuvants, Immunologic pharmacology
Adult
Aged
CD4-Positive T-Lymphocytes drug effects
CD4-Positive T-Lymphocytes metabolism
CD8-Positive T-Lymphocytes drug effects
CD8-Positive T-Lymphocytes metabolism
Case-Control Studies
Cell Count
Female
Humans
Imiquimod pharmacology
Immunotherapy
Middle Aged
Myeloid Cells drug effects
Myeloid Cells metabolism
Neoplasm Grading
Squamous Intraepithelial Lesions immunology
Squamous Intraepithelial Lesions pathology
Treatment Outcome
Tumor Microenvironment drug effects
Vulvar Neoplasms immunology
Vulvar Neoplasms pathology
Adjuvants, Immunologic administration & dosage
Imiquimod administration & dosage
Squamous Intraepithelial Lesions drug therapy
Vulvar Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0215
- Volume :
- 147
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 32574376
- Full Text :
- https://doi.org/10.1002/ijc.33168