Cancer testis antigen PRAME: An anti-cancer target with immunomodulatory potential.
Antigens, Neoplasm
/ genetics
Biomarkers, Tumor
Chemotaxis
/ genetics
Computational Biology
/ methods
Cytokines
/ metabolism
Databases, Genetic
Disease Management
Disease Susceptibility
Gene Expression Profiling
Gene Ontology
Humans
Immunomodulation
/ genetics
Immunophenotyping
Lymphocyte Activation
/ immunology
Lymphocytes
/ immunology
Neoplasms
/ etiology
Prognosis
Transcriptome
PRAME
breast cancer
immune activation
immune checkpoints
immunotherapy
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
29
08
2021
received:
25
05
2021
accepted:
20
09
2021
pubmed:
7
10
2021
medline:
16
3
2022
entrez:
6
10
2021
Statut:
ppublish
Résumé
PReferentially expressed Antigen in Melanoma (PRAME) is a cancer testis antigen with restricted expression in somatic tissues and re-expression in poor prognostic solid tumours. PRAME has been extensively investigated as a target for immunotherapy, however, its role in modulating the anti-tumour immune response remains largely unknown. Here, we show that PRAME tumour expression is associated with worse survival in the TCGA breast cancer cohort, particularly in immune-unfavourable tumours. Using direct and indirect co-culture models, we found that PRAME overexpressing MDA-MB-468 breast cancer cells inhibit T cell activation and cytolytic potential, which could be partly restored by silencing of PRAME. Furthermore, silencing of PRAME reduced expression of several immune checkpoints and their ligands, including PD-1, LAG3, PD-L1, CD86, Gal-9 and VISTA. Interestingly, silencing of PRAME induced cancer cell killing to levels similar to anti-PD-L1 atezolizumab treatment. Comprehensive analysis of soluble inflammatory mediators and cancer cell expression of immune-related genes showed that PRAME tumour expression can suppress the expression and secretion of multiple pro-inflammatory cytokines, and mediators of T cell activation, differentiation and cytolysis. Together, our data indicate that targeting of PRAME offers a potential, novel dual therapeutic approach to specifically target tumour cells and regulate immune activation in the tumour microenvironment.
Identifiants
pubmed: 34612587
doi: 10.1111/jcmm.16967
pmc: PMC8581324
doi:
Substances chimiques
Antigens, Neoplasm
0
Biomarkers, Tumor
0
Cytokines
0
PRAME protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10376-10388Informations de copyright
© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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