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. 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.
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.
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.
Authors: Lauren Van Der Kraak; Gaurav Goel; Rajeev Dhupar; Michael T Lotze; Krishnaveni Ramanan; Christof Kaltenmeier; Lin Zhang; Daniel P Normolle; Gordon J Freeman; Daolin Tang; Katie S Nason; Jon M Davison; James D Luketich Journal: J Immunother Cancer Date: 2016-10-18 Impact factor: 13.751
Authors: Andrea B Apolo; Jeffrey R Infante; Ani Balmanoukian; Manish R Patel; Ding Wang; Karen Kelly; Anthony E Mega; Carolyn D Britten; Alain Ravaud; Alain C Mita; Howard Safran; Thomas E Stinchcombe; Marko Srdanov; Arnold B Gelb; Michael Schlichting; Kevin Chin; James L Gulley Journal: J Clin Oncol Date: 2017-04-04 Impact factor: 44.544
Authors: Edwin R Parra; Pamela Villalobos; Carmen Behrens; Mei Jiang; Apar Pataer; Stephen G Swisher; William N William; Jiexin Zhang; Jack Lee; Tina Cascone; John V Heymach; Marie-Andrée Forget; Cara Haymaker; Chantale Bernatchez; Neda Kalhor; Annikka Weissferdt; Cesar Moran; Jianjun Zhang; Ara Vaporciyan; Don L Gibbons; Boris Sepesi; Ignacio I Wistuba Journal: J Immunother Cancer Date: 2018-06-06 Impact factor: 13.751
Authors: Charlotte Pilard; Marie Ancion; Philippe Delvenne; Guy Jerusalem; Pascale Hubert; Michael Herfs Journal: Br J Cancer Date: 2021-06-10 Impact factor: 9.075