Checkpoint Genes at the Cancer Side of the Immunological Synapse in Bladder Cancer.


Journal

Translational oncology
ISSN: 1936-5233
Titre abrégé: Transl Oncol
Pays: United States
ID NLM: 101472619

Informations de publication

Date de publication:
Feb 2020
Historique:
received: 28 06 2019
revised: 30 09 2019
accepted: 31 10 2019
pubmed: 24 12 2019
medline: 24 12 2019
entrez: 24 12 2019
Statut: ppublish

Résumé

Immune checkpoint inhibitors have revolutionized cancer therapy, but not all cancers respond to the currently available drugs, and even within cancers considered responsive to such modality, response rates range between 15 and 40%, depending on the cancer type, the line of treatment, and yet unknown clinical/molecular factors. Coordinated expression of checkpoint proteins was shown to occur on T cells, probably allowing fine-tuning of the signal transmitted to the cell. We performed a bioinformatic analysis of the expression of putative checkpoint mRNAs at the cancer side of the immunological synapse from the bladder cancer tumorgenome atlas (TCGA) database. Fifteen mRNAs, corresponding to both coinhibitory and costimulatory checkpoints, were shown to be expressed above a designated threshold. Of these, seven mRNAs were found to be coexpressed: CD277, PD-1L, CD48, CD86, galectin-9, TNFRSF14 (HVEM), and CD40. The expression of 2 of these mRNAs-BTN3A1 (CD277) and TNFRSF14 (HVEM)-was positively correlated with overall survival in the TCGA database. All these seven mRNA share putative binding sites of a few transcription factors (TFs). Of these, the expression of the TF BACH-2 was positively correlated with the expression of checkpoint mRNAs from the network. This suggests a joint transcriptional regulation on the expression of checkpoint mRNAs at the bladder tumor side of the immunological synapse.

Identifiants

pubmed: 31869744
pii: S1936-5233(19)30338-9
doi: 10.1016/j.tranon.2019.10.018
pmc: PMC6931203
pii:
doi:

Types de publication

Journal Article

Langues

eng

Pagination

193-200

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Paula Dobosz (P)

Oncology Institute and Cancer Research Centre, Sheba Medical Centre Hospital, Tel Hashomer, Ramat Gan, Israel.

Przemysław A Stempor (PA)

School of Life Sciences, Gurdon Institute, Department of Genetics, Tennis Court Rd, Cambridge, UK; The Wellcome Trust/CRUK Gurdon Institute, University of Cambridge, Tennis Court Rd, Cambridge, UK; Department of Genetics, University of Cambridge, Downing Street, Cambridge, UK.

Jason Roszik (J)

Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Centre, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Centre, USA.

Amir Herman (A)

Orthopedic Department, Assuta Medical Center, Ashdod, Israel.

Adi Layani (A)

Oncology Institute and Cancer Research Centre, Sheba Medical Centre Hospital, Tel Hashomer, Ramat Gan, Israel.

Raanan Berger (R)

Oncology Institute and Cancer Research Centre, Sheba Medical Centre Hospital, Tel Hashomer, Ramat Gan, Israel; Oncology Department, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Dror Avni (D)

Oncology Institute and Cancer Research Centre, Sheba Medical Centre Hospital, Tel Hashomer, Ramat Gan, Israel.

Yechezkel Sidi (Y)

Oncology Institute and Cancer Research Centre, Sheba Medical Centre Hospital, Tel Hashomer, Ramat Gan, Israel; Oncology Department, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Raya Leibowitz-Amit (R)

Oncology Institute and Cancer Research Centre, Sheba Medical Centre Hospital, Tel Hashomer, Ramat Gan, Israel; Oncology Department, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: rayal@shamir.gov.il.

Classifications MeSH