Title:Targeting the Programmed Cell Death-1 Pathway in Genitourinary Tumors: Current Progress and Future Perspectives
Volume: 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*
Affiliation:
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 West 11th Street, IUHPL Room 4010, Indianapolis, IN 46202,United States
Keywords:
Genitourinary tumors, bladder, kidney, immunotherapy, immune checkpoint blockade, PD-1/PD-L1 biomarkers.
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.
