The Δ133p53β Isoform Promotes an Immunosuppressive Environment Leading to Aggressive Prostate Cancer

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2019 Aug 22

PMID 31431617

Citations 35

Authors

Marina Kazantseva

Sunali Mehta

Ramona A Eiholzer

Gregory Gimenez

Sara Bowie

Hamish Campbell

Ashley L Reily-Bell

Imogen Roth

Sankalita Ray

Catherine J Drummond

Glen Reid

Sebastien M Joruiz

Anna Wiles

Helen R Morrin

Karen L Reader

Noelyn A Hung

Margaret A Baird

Tania L Slatter

Antony W Braithwaite

Affiliations

Soon will be listed here.

Abstract

Prostate cancer is the second most common cancer in men, for which there are no reliable biomarkers or targeted therapies. Here we demonstrate that elevated levels of Δ133TP53β isoform characterize prostate cancers with immune cell infiltration, particularly T cells and CD163+ macrophages. These cancers are associated with shorter progression-free survival, Gleason scores ≥ 7, and an immunosuppressive environment defined by a higher proportion of PD-1, PD-L1 and colony-stimulating factor 1 receptor (CSF1R) positive cells. Consistent with this, RNA-seq of tumours showed enrichment for pathways associated with immune signalling and cell migration. We further show a role for hypoxia and wild-type p53 in upregulating Δ133TP53 levels. Finally, AUC analysis showed that Δ133TP53β expression level alone predicted aggressive disease with 88% accuracy. Our data identify Δ133TP53β as a highly accurate prognostic factor for aggressive prostate cancer.

Citing Articles

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