Login to Access Video or Poster Abstract: MP44-05
Sources of Funding: This research was supported in part by the John P. Hanson Foundation for Cancer and Cellular Research. The results shown here are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/

Introduction

Currently, only 30% of patients respond to therapy with checkpoint inhibitors PD-1/PD-L1. Exploration of other members of the B7-CD28 family may provide additional targets for immunotherapy. B7-H4 (VTCN1) has previously been demonstrated to be associated with survival in renal cell carcinoma and breast cancer, but little is known regarding its expression in bladder cancer.

Methods

Mutational, RNAseq, and clinical data from The Cancer Genome Atlas (TCGA) provisional bladder urothelial carcinoma dataset (n=408) was downloaded from cBioPortal (http://www.cbioportal.org/). Normalized RNAseq data was correlated with the number of non-synonymous mutations using Spearman's correlation. Overall survival of patients with overexpression (z>2) of immune checkpoints was compared using Kaplan-Meyer analysis. TCGA samples were subtyped using the original TCGA molecular subtypes 1-4 (n=131). Expression of immune checkpoints was compared between subgroups using ANOVA. Statistical analysis was performed using R and GraphPad Prism.

Results

Overexpression (z>2) of B7-H4 is associated with poor survival (Figure 1). Expression of B7-H4 is not associated with expression of CD8A, or with the number of non-synonymous mutations, unlike PD-1, PD-L1, PD-L2, CTLA-4, TIM-3, and LAG-3. Expression of B7-H4 is highest in TCGA subtype II (luminal / p-53-like), unlike PD-1, PD-L1, CTLA-4, TIM-3, and LAG-3 (TCGA subtype IV, basal / claudin-low) (Figure 2)._x000D_

Conclusions

Overexpression of B7-H4, a member of the B7-CD28 co-stimulatory family, is associated with poor survival in bladder urothelial carcinoma. B7-H4 is highly expressed in TCGA Subtype II (luminal), unlike PD-L1, which is highly expressed in Subtype IV (basal / claudin-low). Further study of B7-H4 and its function in bladder cancer is needed, but it may be a promising target for immunotherapy, especially for patients who do not respond to PD-L1 therapy.

Funding

This research was supported in part by the John P. Hanson Foundation for Cancer and Cellular Research. The results shown here are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/