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Cancer testis antigen PRAME: An anti‐cancer target with immunomodulatory potential

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submitted on 2023-03-15, 08:05 and posted on 2023-03-15, 11:07 authored by Adviti Naik, Remy Thomas, Ghaneya Al‐Khadairi, Rim Bacha, Wouter Hendrickx, Julie Decock

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.

Other Information

Published in: Journal of Cellular and Molecular Medicine
License: http://creativecommons.org/licenses/by/4.0/
See article on publisher's website: http://dx.doi.org/10.1111/jcmm.16967

History

Language

  • English

Publisher

Wiley

Publication Year

  • 2021

Institution affiliated with

  • Hamad Bin Khalifa University
  • Qatar Biomedical Research Institute

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