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


Montironi, Rodolfo; Cheng, Liang; Moch, Holger; Lopez-Beltran, Antonio; Scarpelli, Marina; Massari, Francesco; Fiorentino, Michelangelo; Ciccarese, Chiara; Koch, Michael; Kaimakliotis, Hristos Z; Wang, Lisha; Pili, Roberto; Mann, Steven A (2017). Targeting the Programmed Cell Death-1 Pathway in Genitourinary Tumors: Current Progress and Future Perspectives. Current Drug Metabolism, 18:Epub ahead of print.

Abstract

Immune checkpoint inhibitors have revolutionized the treatment 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. 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 RCC and urothelial carcinoma. Each FDA-approved PD-1/PD-L1 drug is paired with a PD-L1 immunohistochemistry (IHC) assay. The majority of PD-1/PD-L1 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. 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. RCC has been the most studied of the genitourinary malignancies for PD-L1 expression. The atezolizumab-approved ICH 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.

Abstract

Immune checkpoint inhibitors have revolutionized the treatment 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. 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 RCC and urothelial carcinoma. Each FDA-approved PD-1/PD-L1 drug is paired with a PD-L1 immunohistochemistry (IHC) assay. The majority of PD-1/PD-L1 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. 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. RCC has been the most studied of the genitourinary malignancies for PD-L1 expression. The atezolizumab-approved ICH 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:18 May 2017
Deposited On:13 Jun 2017 12:47
Last Modified:14 Jun 2017 01:03
Publisher:Bentham Science Publishers Ltd.
ISSN:1389-2002
Publisher DOI:https://doi.org/10.2174/1389200218666170518162500
PubMed ID:28524003

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