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

Paula Dobosz, Przemysław A. Stempor, Jason Roszik, Amir Herman, Adi Layani, Raanan Berger, Dror Avni, Yechezkel Sidi, Raya Leibowitz-Amit

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)193-200
Number of pages8
JournalTranslational Oncology
Volume13
Issue number2
DOIs
StatePublished - 1 Feb 2020
Externally publishedYes

Fingerprint

Dive into the research topics of 'Checkpoint Genes at the Cancer Side of the Immunological Synapse in Bladder Cancer'. Together they form a unique fingerprint.

Cite this