Expression of PDL1 (B7-H1) Before and After Neoadjuvant Chemotherapy in Urothelial Carcinoma

Andrew S McDaniel; Ajjai Alva; Tianyu Zhan; Hong Xiao; Xuhong Cao; Amy Gursky; Javed Siddiqui; Arul M Chinnaiyan; Hui Jiang; Cheryl T Lee; Rohit Mehra

doi:10.1016/j.euf.2015.03.004

Expression of PDL1 (B7-H1) Before and After Neoadjuvant Chemotherapy in Urothelial Carcinoma

Eur Urol Focus. 2016 Feb;1(3):265-268. doi: 10.1016/j.euf.2015.03.004. Epub 2015 Jun 6.

Authors

Andrew S McDaniel¹, Ajjai Alva², Tianyu Zhan³, Hong Xiao⁴, Xuhong Cao⁵, Amy Gursky⁶, Javed Siddiqui⁵, Arul M Chinnaiyan⁷, Hui Jiang³, Cheryl T Lee⁸, Rohit Mehra⁹

Affiliations

¹ Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
² Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA.
³ Department of Biostatistics, University of Michigan School of Public Health.
⁴ Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
⁵ Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI, USA.
⁶ Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
⁷ Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Howard Hughes Medical Institute, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
⁸ Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA.
⁹ Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, USA; Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: mrohit@med.umich.edu.

PMID: 28723397
DOI: 10.1016/j.euf.2015.03.004

Abstract

Expression of the costimulatory ligand PDL1 (B7-H1) on tumors allows escape from antitumor immunity. PDL1 expression has been reported in urothelial carcinoma (UC), suggesting it could be used as an immunotherapy target. We investigated the impact of cytotoxic neoadjuvant chemotherapy (NAC) on PDL1 expression in UC. Immunohistochemical staining for PDL1 was performed using an anti-B7-H1 monoclonal antibody (5H1) on a tissue microarray with matched pre-NAC and post-NAC UC samples from 40 patients treated between 1999 and 2011. PDL1 expression was significantly higher in post-NAC specimens than in matched pre-NAC specimens (p=0.0235, Wilcoxen's signed rank test). PDL1 expression in pre-NAC tissue did not correlate with clinical or pathologic stage but was associated with recurrence free survival. The increase in PDL1 expression following NAC in our limited cohort has potential to guide optimal combination and sequencing of immune and cytotoxic therapies in UC patients.

Patient summary: We investigated the relationship between levels of the drug target PDL1 before and after chemotherapy in patients with bladder cancer. We found that levels of PDL1 increased following chemotherapy. We conclude that this information may help doctors in optimizing the sequence of therapies in bladder cancer.

Keywords: B7-H1; Immunotherapy; Neoadjuvant chemotherapy; PDL1; Urothelial carcinoma.