Distinct tumor microenvironment profiles characterize regressive versus progressive anal precancers
iScience, vol. 29, pp. 117404
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.
Authors 10
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Amsterdam UMC Location University of Amsterdam · Cancer Center Amsterdam · Amsterdam institute for Immunology and Infectious Diseases · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam Institute for Immunology & Infectious Diseases (AI&I), Amsterdam, the Netherlands
Amsterdam UMC, Location University of Amsterdam, Department of Dermatology, Meibergdreef 9, Amsterdam, the Netherlands
Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Pathology, Boelelaan 1117, Amsterdam, the Netherlands
Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center, Department of Pathology, Albinusdreef 2, 2333 ZA Leiden, the Netherlands
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Cancer Center Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Pathology, Boelelaan 1117, Amsterdam, the Netherlands
Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands
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Amsterdam Public Health · Amsterdam University Medical Centers · Cancer Center Amsterdam · University of Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Pathology, Boelelaan 1117, Amsterdam, the Netherlands
Amsterdam UMC, VU University of Amsterdam, Department of Epidemiology and Data Science, Amsterdam Public Health, Meibergdreef 9, Amsterdam, the Netherlands
Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands
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Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Pathology, Boelelaan 1117, Amsterdam, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Leiden University Medical Center, Department of Pathology, Albinusdreef 2, 2333 ZA Leiden, the Netherlands
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Amsterdam UMC Location University of Amsterdam · Amsterdam institute for Immunology and Infectious Diseases
Affiliation as printed
Amsterdam Institute for Immunology & Infectious Diseases (AI&I), Amsterdam, the Netherlands
Amsterdam UMC Location University of Amsterdam, Department of Internal Medicine, Division of Infectious Diseases, Meibergdreef 9, Amsterdam, the Netherlands
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Amsterdam UMC Location University of Amsterdam · Cancer Center Amsterdam · Amsterdam institute for Immunology and Infectious Diseases
Affiliation as printed
Amsterdam Institute for Immunology & Infectious Diseases (AI&I), Amsterdam, the Netherlands
Amsterdam UMC, Location University of Amsterdam, Department of Dermatology, Meibergdreef 9, Amsterdam, the Netherlands
Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands
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Cancer Center Amsterdam · Amsterdam UMC Location Vrije Universiteit Amsterdam
Affiliation as printed
Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Pathology, Boelelaan 1117, Amsterdam, the Netherlands
Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, the Netherlands
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Henry J.C. de Vries corresponding
Amsterdam UMC Location University of Amsterdam · Amsterdam Institute for Global Health and Development · GGD Amsterdam · Amsterdam institute for Immunology and Infectious Diseases
Affiliation as printed
Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands
Amsterdam Institute for Immunology & Infectious Diseases (AI&I), Amsterdam, the Netherlands
Amsterdam UMC, Location University of Amsterdam, Department of Dermatology, Meibergdreef 9, Amsterdam, the Netherlands
Center for Sexual Health, Department of Infectious Diseases, Public Health Service Amsterdam, Amsterdam, the Netherlands
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