Intraepithelial CD15 infiltration identifies high-grade anal dysplasia in people with HIV
Burgos, Joaquín (Vall d'Hebron Institut de Recerca (VHIR))
Benítez-Martínez, Aleix (Vall d'Hebron Institut de Recerca (VHIR))
Mancebo, Cristina (Vall d'Hebron Institut de Recerca (VHIR))
Massana, Núria (Vall d'Hebron Institut de Recerca (VHIR))
Astorga-Gamaza, Antonio (Vall d'Hebron Institut de Recerca (VHIR))
Castellvi, Josep (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques)
Landolfi, Stefania (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques)
Curran, Adrian (Vall d'Hebron Institut de Recerca (VHIR))
García Pérez, Jorge N. (Vall d'Hebron Institut de Recerca (VHIR))
Falcó, Vicenç (Vall d'Hebron Institut de Recerca (VHIR))
Buzón, Maria José (Vall d'Hebron Institut de Recerca (VHIR))
Genescà Ferrer, Meritxell (Vall d'Hebron Institut de Recerca (VHIR))

Data:	2024
Resum:	Men who have sex with men (MSM) with HIV are at high risk for squamous intraepithelial lesion (SIL) and anal cancer. Identifying local immunological mechanisms involved in the development of anal dysplasia could aid treatment and diagnostics. Here, we studied 111 anal biopsies obtained from 101 MSM with HIV, who participated in an anal screening program. We first assessed multiple immune subsets by flow cytometry, in addition to histological examination, in a discovery cohort. Selected molecules were further evaluated by immunohistochemistry in a validation cohort. Pathological samples were characterized by the presence of resident memory T cells with low expression of CD103 and by changes in natural killer cell subsets, affecting residency and activation. Furthermore, potentially immunosuppressive subsets, including CD15 + CD16 + mature neutrophils, gradually increased as the anal lesion progressed. Immunohistochemistry verified the association between the presence of CD15 in the epithelium and SIL diagnosis for the correlation with high-grade SIL. A complex immunological environment with imbalanced proportions of resident effectors and immune-suppressive subsets characterized pathological samples. Neutrophil infiltration, determined by CD15 staining, may represent a valuable pathological marker associated with the grade of dysplasia. Assessment of changes in relevant anal dysplasia-associated mucosal immune subsets provides potential targets for immunotherapy and a complementary biomarker for current diagnostics.
Ajuts:	Ministerio de Economía y Competitividad PI16/00736 Ministerio de Economía y Competitividad PI20/00160 Ministerio de Economía y Competitividad RD16/0025/0007 Fundació la Marató de TV3 20181410FMTV3
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Immunology ; Infectious disease ; Adaptive immunity ; Cervical cancer ; Innate immunity
Publicat a:	JCI insight, Vol. 9 (june 2024) , ISSN 2379-3708

DOI: 10.1172/jci.insight.175251
PMID: 38900571

16 p, 3.1 MB

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