CD52 mRNA expression predicts prognosis and response to immune checkpoint blockade in melanoma.
CD52
PD-1
immune checkpoint blockade
immunotherapy
melanoma
prognosis
therapy response
tumor microenvironment
Journal
Pigment cell & melanoma research
ISSN: 1755-148X
Titre abrégé: Pigment Cell Melanoma Res
Pays: England
ID NLM: 101318927
Informations de publication
Date de publication:
17 Nov 2023
17 Nov 2023
Historique:
revised:
27
09
2023
received:
25
07
2023
accepted:
29
10
2023
medline:
17
11
2023
pubmed:
17
11
2023
entrez:
17
11
2023
Statut:
aheadofprint
Résumé
The immune-modulating protein CD52 attenuates lymphocyte function and is associated with autoimmune disorders, for example, multiple sclerosis (MS). CD52 represents a therapeutic target in MS and chronic lymphocytic leukemia (CLL). Its expression has prognostic and predictive value in CLL and is prognostic in breast cancer. Its significance in melanoma is unclear. We analyzed CD52 mRNA expression data from tumor bulk tissues of N = 445 untreated melanoma patients from The Cancer Genome Atlas (TCGA) Research Network and of N = 121 melanoma patients undergoing anti-PD-1 immune checkpoint blockade (ICB) with regard to outcome (overall survival [OS], disease control [DC], and progression-free survival [PFS]), single-cell RNA-Seq data of N = 4645 cells from N = 19 melanoma tissues, and N = 15,457 cells from normal skin provided by N = 5 donors. Higher CD52 mRNA expression was associated with favorable OS (hazard ratio (HR) = 0.820, [95% CI 0.734-0.916], p < .001) in non-ICB-treated melanoma and with PFS (HR = 0.875, [95% CI 0.775-0.989], p = .033) and DC (p = .005) in ICB-treated melanoma. CD52 expression correlated significantly with distinct immune cell subsets and correlated negatively with immune checkpoint expression in T cells. Moreover, our results suggest CD52 expression by a certain type of tissue-resident macrophages. CD52 mRNA was expressed in a small subgroup (8%) of immune checkpoint coexpressing melanoma cells. CD52 expression is associated with features of ICB response in melanoma. Concomitant ICB and anti-CD52 treatment requires critical review.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : University Hospital Bonn, BONFOR
ID : O-105.0069
Organisme : University Hospital Bonn, BONFOR
ID : O-105.0072
Organisme : University Hospital Bonn, BONFOR
ID : O-138.0010
Organisme : University Hospital Bonn, BONFOR
ID : O-138.0011
Informations de copyright
© 2023 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.
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