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Cancer testis antigen PRAME: An anti‐cancer target with immunomodulatory potential
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2021
- Publisher :
- John Wiley and Sons Inc., 2021.
-
Abstract
- 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.
- Subjects :
- Chemotaxis
Gene Expression Profiling
Computational Biology
Disease Management
Original Articles
immune checkpoints
Lymphocyte Activation
Prognosis
immune activation
Immunophenotyping
Immunomodulation
breast cancer
Gene Ontology
Antigens, Neoplasm
PRAME
Neoplasms
Databases, Genetic
Biomarkers, Tumor
Cytokines
Humans
Original Article
immunotherapy
Disease Susceptibility
Lymphocytes
Transcriptome
Subjects
Details
- Language :
- English
- ISSN :
- 15824934 and 15821838
- Volume :
- 25
- Issue :
- 22
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.pmid..........06b221b24c2bb6cfd91cef6dd1353da6