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Targeting the Programmed Cell Death-1 Pathway in Genitourinary Tumors: Current Progress and Future Perspectives

[ Vol. 18 , Issue. 8 ]

Author(s):

Steven A. Mann, Antonio Lopez-Beltran, Francesco Massari, Roberto Pili, Michelangelo Fiorentino, Michael O. Koch, Hristos Z. Kaimakliotis, Lisha Wang, Marina Scarpelli, Chiara Ciccarese, Holger Moch, Rodolfo Montironi and Liang Cheng*   Pages 700 - 711 ( 12 )

Abstract:


Background: Immune checkpoint inhibitors have revolutionized the treatment of many malignancies with over a dozen new United States Food and Drug Administration (FDA) approvals in the past six years. Due to the combination of potent treatment success and potentially deadly adverse effects from immune checkpoint inhibitors, gathering prognostic and predictive information about FDA-indicated tumors is prudent.

Method: PD-L1 expression is a poor prognostic factor and predictive of better responses from both PD-1 and PD-L1 inhibitors in a variety of tumor types including Renal Cell Carcinoma (RCC) and urothelial carcinoma. Each FDAapproved PD-1/PD-L1 drug is paired with a PD-L1 Immunohistochemistry (IHC) assay. The majority of PD-1/PDL1 inhibitor clinical trials use proprietary IHC antibodies with undefined validation data. Thus, there is need for improved knowledge and application of PD-1/PD-L1 IHC biomarkers. There is a wealth of recent publications using antibody clones to characterize tumor PD-1/PD-L1 expression profiles.

Results: PD-1 is expressed on lymphocytes. PD-L1 is expressed on both tumor cells and immune cells. IHC staining appears in membranous fashion. A cutoff of at least 5% tumor cell PD-L1 staining for positivity has worked for most studies. Caution should be observed when employing tissue microarray techniques.

Conclusion: RCC has been the most studied of the genitourinary malignancies for PD-L1 expression. The atezolizumab- approved IHC assay is unique in that only immune cell staining is quantified for the use of this assay in urothelial carcinoma. With familiarity of the current FDA guidelines, published medical literature, and general immunohistochemical considerations, the use of immune checkpoint biomarkers can continue to flourish.

Keywords:

Genitourinary tumors, bladder, kidney, immunotherapy, immune checkpoint blockade, PD-1/PD-L1 biomarkers.

Affiliation:

Departments of Pathology, Indiana University School of Medicine, Indianapolis, Unit of Anatomical Pathology, Faculty of Cordoba University, Cordoba, Spain and Champalimaud Clinical Center, Lisbon, Division of Oncology, S.Orsola-Malpighi Hospital, Bologna, Departments of Internal Medicine Indiana University School of Medicine, Indianapolis, Pathology Service, Addarii Institute of Oncology, S. Orsola-Malpighi Hospital, Bologna, Departments of Urology, Indiana University School of Medicine, Indianapolis, Departments of Urology, Indiana University School of Medicine, Indianapolis, Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, Michigan, Institute of Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Medical Oncology, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Institute of Surgical Pathology, University of Zurich, Zurich, Institute of Pathological Anatomy and Histopathology, School of Medicine, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 West 11th Street, IUHPL Room 4010, Indianapolis, IN 46202

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