Article
Urology & Nephrology
Mathieu Rouanne, Camelia Radulescu, Julien Adam, Yves Allory
Summary: This review critically evaluated the role of PD-L1 as a predictive biomarker for response to immune checkpoint blockade in patients with urothelial bladder carcinoma, discussing its limitations in clinical practice. Evidence data regarding PD-L1 as a predictive biomarker were detailed, including companion diagnostic assays and scoring methods. Use of PD-(L)1 monoclonal antibodies are restricted to patients with PD-L1 positive status in certain clinical settings, while identification of biomarkers with high negative predictive value is crucial for non-responders.
WORLD JOURNAL OF UROLOGY
(2021)
Article
Oncology
Dimitrios Goutas, Kostas Palamaris, Anastasios Stofas, Nektarios Politakis, Antonia Despotidi, Ioanna Giannopoulou, Nikolaos Goutas, Dimitrios Vlachodimitropoulos, Nikolaos Kavantzas, Andreas C. Lazaris, Hariklia Gakiopoulou
Summary: Our study aimed to stratify bladder cancer patients into molecular subtypes using a simple and inexpensive immunohistochemical algorithm, and investigate the associations with PD-L1 expression. The heterogeneity in clinical outcomes of bladder cancer has highlighted different biological subtypes. Immunotherapy drugs targeting PD-1/PD-L1 have been developed, but there is a lack of predictive biomarkers. We categorized patients' tumors into molecular subtypes and attempted to predict their response to anti-PD-L1 therapy based on their molecular phenotype. The deficiency of mismatch repair proteins (MMR) was also examined.
Article
Multidisciplinary Sciences
Georgi Tosev, Wasilijiang Wahafu, Philipp Reimold, Ivan Damgov, Constantin Schwab, Cem Aksoy, Adam Kaczorowski, Albrecht Stenzinger, Joanne Nyarangi-Dix, Markus Hohenfellner, Stefan Duensing
Summary: Urine PD-L1 levels may serve as a potential novel biomarker for the early detection, prediction, and therapeutic monitoring of bladder UC patients, requiring further prospective and independent studies to validate its value.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Aleksandra Semeniuk-Wojtas, Magdalena Modzelewska, Karolina Poddebniak-Strama, Sylwia Kolaczynska, Arkadiusz Lubas, Barbara Gornicka, Anna Jakiela, Rafal Stec
Summary: The infiltration of CD4 and CD20 cells in the tumor microenvironment, as well as the expression of PD-L1 on tumor cells, independently affect the risk of bladder cancer recurrence. Patients with weak CD4 cell infiltration and severe CD20 cell infiltration belong to the low-risk recurrence group.
Review
Biochemistry & Molecular Biology
Florus C. de Jong, Vera C. Rutten, Tahlita C. M. Zuiverloon, Dan Theodorescu
Summary: PD-1/PD-L1 immune checkpoint inhibitors show promise in high-risk non-muscle invasive bladder cancer and muscle-invasive bladder cancer, but challenges such as biomarkers for response stratification and potentially synergistic combination therapy regimens with PD-1/PD-L1 blockade need to be addressed to improve patient outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Richard S. P. Huang, James Haberberger, Lukas Harries, Eric Severson, Daniel L. Duncan, N. Lynn Ferguson, Amanda Hemmerich, Claire Edgerly, Karthikeyan Murugesan, Jinpeng Xiao, Deborah McEwan, Oliver Holmes, Matthew Hiemenz, Jeffrey Venstrom, Julia A. Elvin, James Creeden, Douglas I. Lin, Jeffrey S. Ross, Shakti H. Ramkissoon
Summary: This study found genomic differences between PD-L1(positive) and PD-L1(negative) urothelial carcinomas, providing a framework for future clinical investigation. Additionally, differences in PD-L1 positivity based on sample collection sites were observed, which could influence sample selection for PD-L1 testing in patients with urothelial carcinoma.
Article
Immunology
Enrico Munari, Giulia Querzoli, Matteo Brunelli, Marcella Marconi, Marco Sommaggio, Marco A. Cocchi, Guido Martignoni, George J. Netto, Anna Calio, Linda Quatrini, Francesca R. Mariotti, Claudio Luchini, Ilaria Girolami, Albino Eccher, Diego Segala, Francesco Ciompi, Giuseppe Zamboni, Lorenzo Moretta, Giuseppe Bogina
Summary: This study investigated the application of different PD-L1 assays in advanced urothelial carcinoma and evaluated their impact on patient selection for immunotherapy. The results showed that the 22C3 and SP263 assays have comparable analytical performance, while the SP142 assay has divergent staining results, which may have important implications for selecting the appropriate treatment method.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Gottfrid Sjodahl, Pontus Eriksson, Karin Holmsten, Johan Abrahamsson, Mattias Hoglund, Carina Bernardo, Anders Ullen, Fredrik Liedberg
Summary: This study finds that molecular subtypes of urothelial bladder cancer are associated with specific metastatic sites. The Basal/squamous subtype is less likely to metastasize to bone, while the Urothelial-like subtype has an increased tendency to metastasize to bone. The Genomically unstable subtype is less likely to metastasize to the lungs, but is more likely to metastasize to atypical sites, including the brain.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Oncology
Antonio Lopez-Beltran, Fernando Lopez-Rios, Rodolfo Montironi, Sophie Wildsmith, Markus Eckstein
Summary: The workshops aimed to develop recommendations for best practice approaches to PD-L1 testing in UC, emphasizing the importance of robust control of analytical standards, clear communication for interpretation and reporting of PD-L1 results. In addition, a test request form for pathology laboratories was developed to facilitate communication between clinicians and pathologists for fast and high-quality test results. Novel biomarkers for immuno-oncology agents in UC were briefly discussed in the era of personalized medicine.
Review
Immunology
Quanqing Tang, Shihao Li, Gaozhen Huang, Hongwei Liu
Summary: Urothelial carcinoma (UC) is a common malignant tumor. Platinum-based chemotherapy has been the standard treatment for metastatic UC, but immune checkpoint inhibitors (ICIs) offer hope for patients unfit for platinum therapy.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Cell Biology
Fan Zhang, Jiayu Liang, Dechao Feng, Shengzhuo Liu, Jiapei Wu, Yongquan Tang, Zhihong Liu, Yiping Lu, Xianding Wang, Xin Wei
Summary: The energy metabolism-associated subtypes of bladder urothelial carcinoma are closely related to the immune microenvironment, chemotherapy resistance, and prognosis. An energy metabolism-related gene signature has been developed to predict the survival of patients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Oncology
Sen Yan, Han Zeng, Kaifeng Jin, Fei Shao, Zhaopei Liu, Yuan Chang, Yiwei Wang, Yu Zhu, Zewei Wang, Le Xu, Jiejie Xu
Summary: The expression of NKG2A and PD-L1 together can be used as a combinatorial biomarker to predict the therapeutic response to immune checkpoint blockade in patients with muscle-invasive bladder cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Biotechnology & Applied Microbiology
Shiva Izadi, Simon Gumpelmair, Pedro Coelho, Henrique O. Duarte, Joana Gomes, Judith Leitner, Vinny Kunnummel, Lukas Mach, Celso A. Reis, Peter Steinberger, Alexandra Castilho
Summary: Immune checkpoint blocking therapy targeting the PD-1/PD-L1 inhibitory signalling pathway has shown promising results in cancer treatment. This study produced different variants of Durvalumab using Nicotiana benthamiana and found that they exhibited similar functions to the therapeutic antibody, including binding to PD-L1, blocking PD-1/PD-L1 signaling, and interacting with FcRn and Fc gamma receptors.
PLANT BIOTECHNOLOGY JOURNAL
(2023)
Article
Oncology
Niklas Kluemper, Lennert Wuest, Jonas Saal, Damian J. Ralser, Romina Zarbl, Jonas Jarczyk, Johannes Breyer, Danijel Sikic, Bernd Wullich, Christian Bolenz, Florian Roghmann, Michael Hoelzel, Manuel Ritter, Sebastian Strieth, Arndt Hartmann, Philipp Erben, Ralph M. Wirtz, Jennifer Landsberg, Dimo Dietrich, Markus Eckstein
Summary: This study evaluated the predictive potential of PD-L1 promoter methylation status in immune checkpoint blockade (ICB) treatment of metastatic urothelial carcinoma (mUC). The study found that hypomethylation of the PD-L1 promoter is a promising predictive biomarker for response to ICB in patients with mUC, while PD-L1 protein expression status is not correlated with treatment response and survival.
Article
Oncology
Shiuh-Rong Ho, Yu-Cheng Lee, Michael M. Ittmann, Fang-Tsyr Lin, Keith Syson Chan, Weei-Chin Lin
Summary: The study reveals the tumor suppressor activity of RNF144A in vivo upon carcinogenic insult. Loss of RNF144A promotes the expression of DNA-PKcs, BMI1 and PD-L1, likely contributing to the carcinogen-induced bladder tumorigenesis.
Article
Biochemistry & Molecular Biology
Vasty Osei-Amponsa, Jenna M. Buckwalter, Lauren Shuman, Zongyu Zheng, Hironobu Yamashita, Vonn Walter, Thomas Wildermuth, Justine Ellis-Mohl, Chang Liu, Joshua Warrick, Lisa M. Shantz, Robert P. Feehan, Hikmat AI-Ahmadie, Cathy Mendelsohn, Jay D. Raman, Klaus H. Kaestner, Xue-Ru Wu, David J. DeGraff
Article
Multidisciplinary Sciences
Joshua Warrick, Wenhuo Hu, Hironobu Yamashita, Vonn Walter, Lauren Shuman, Jenna M. Craig, Lan L. Gellert, Mauro A. A. Castro, A. Gordon Robertson, Fengshen Kuo, Irina Ostrovnaya, Judy Sarungbam, Ying-bei Chen, Anuradha Gopalan, Sahussapont J. Sirintrapun, Samson W. Fine, Satish K. Tickoo, Kwanghee Kim, Jasmine Thomas, Nagar Karan, Sizhi Paul Gao, Timothy N. Clinton, Andrew T. Lenis, Timothy A. Chan, Zhiyu Chen, Manisha Rao, Travis J. Hollman, Yanyun Li, Nicholas D. Socci, Shweta Chavan, Agnes Viale, Neeman Mohibullah, Bernard H. Bochner, Eugene J. Pietzak, Min Yuen Teo, Gopa Iyer, Jonathan E. Rosenberg, Dean F. Bajorin, Matthew Kaag, Suzanne B. Merrill, Monika Joshi, Rosalyn Adam, John A. Taylor, Peter E. Clark, Jay D. Raman, Victor E. Reuter, Yu Chen, Samuel A. Funt, David B. Solit, David J. DeGraff, Hikmat A. Al-Ahmadie
Summary: Squamous differentiation in bladder cancer is associated with genomic and immunologic heterogeneity and resistance to immunotherapy. The loss of FOXA1, GATA3, and PPARG expression is involved in lineage plasticity and dysregulation of PD-L1 expression.
NATURE COMMUNICATIONS
(2022)
Correction
Multidisciplinary Sciences
Joshua I. Warrick, Wenhuo Hu, Hironobu Yamashita, Vonn Walter, Lauren Shuman, Jenna M. Craig, Lan L. Gellert, Mauro A. A. Castro, A. Gordon Robertson, Fengshen Kuo, Irina Ostrovnaya, Judy Sarungbam, Ying-bei Chen, Anuradha Gopalan, Sahussapont J. Sirintrapun, Samson W. Fine, Satish K. Tickoo, Kwanghee Kim, Jasmine Thomas, Nagar Karan, Sizhi Paul Gao, Timothy N. Clinton, Andrew T. Lenis, Timothy A. Chan, Ziyu Chen, Manisha Rao, Travis J. Hollman, Yanyun Li, Nicholas D. Socci, Shweta Chavan, Agnes Viale, Neeman Mohibullah, Bernard H. Bochner, Eugene J. Pietzak, Min Yuen Teo, Gopa Iyer, Jonathan E. Rosenberg, Dean F. Bajorin, Matthew Kaag, Suzanne B. Merrill, Monika Joshi, Rosalyn Adam, John A. Taylor, Peter E. Clark, Jay D. Raman, Victor E. Reuter, Yu Chen, Samuel A. Funt, David B. Solit, David J. DeGraff, Hikmat A. Al-Ahmadie
NATURE COMMUNICATIONS
(2022)
Article
Pathology
Lauren Shuman, Jonathan Pham, Thomas Wildermuth, Xue-Ru Wu, Vonn Walter, Joshua I. Warrick, David J. DeGraffy
Summary: Although noninvasive bladder cancers have high recurrence rates, early-stage disease is not well-studied and there is a lack of models to validate the contribution of molecular drivers of bladder tumorigenesis. In this study, a Pik3ca1047R mouse model was generated to understand the role of PIK3CA mutations in bladder tumorigenesis. It was found that Pik3ca1047R can elicit early tumorigenic changes in the urothelium, but progression to invasion may require additional genetic alterations.
AMERICAN JOURNAL OF PATHOLOGY
(2023)