Targeting the programmed cell death-1 pathway in genitourinary tumors: Current progress and future perspectives

Steven A. Mann, Antonio Lopez-Beltran, Francesco Massari, Roberto Pili, Michelangelo Fiorentino, Michael Koch, Hristos Kaimakliotis, Lisha Wang, Marina Scarpelli, Chiara Ciccarese, Holger Moch, Rodolfo Montironi, Liang Cheng

Research output: Contribution to journalReview article

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)700-711
Number of pages12
JournalCurrent Drug Metabolism
Volume18
Issue number8
DOIs
StatePublished - Jan 1 2017

Fingerprint

Cell death
Tumors
Cell Death
Immunohistochemistry
Assays
United States Food and Drug Administration
Cells
Biomarkers
Neoplasms
Staining and Labeling
Renal Cell Carcinoma
Lymphocytes
Antibodies
Microarrays
Carcinoma
Drug Approval
Tissue
Clone Cells
Clinical Trials
Guidelines

Keywords

  • Bladder
  • Genitourinary tumors
  • Immune checkpoint blockade
  • Immunotherapy
  • Kidney
  • PD-1/PD-L1 biomarkers

ASJC Scopus subject areas

  • Pharmacology
  • Clinical Biochemistry

Cite this

Targeting the programmed cell death-1 pathway in genitourinary tumors : Current progress and future perspectives. / Mann, Steven A.; Lopez-Beltran, Antonio; Massari, Francesco; Pili, Roberto; Fiorentino, Michelangelo; Koch, Michael; Kaimakliotis, Hristos; Wang, Lisha; Scarpelli, Marina; Ciccarese, Chiara; Moch, Holger; Montironi, Rodolfo; Cheng, Liang.

In: Current Drug Metabolism, Vol. 18, No. 8, 01.01.2017, p. 700-711.

Research output: Contribution to journalReview article

Mann, SA, Lopez-Beltran, A, Massari, F, Pili, R, Fiorentino, M, Koch, M, Kaimakliotis, H, Wang, L, Scarpelli, M, Ciccarese, C, Moch, H, Montironi, R & Cheng, L 2017, 'Targeting the programmed cell death-1 pathway in genitourinary tumors: Current progress and future perspectives', Current Drug Metabolism, vol. 18, no. 8, pp. 700-711. https://doi.org/10.2174/1389200218666170518162500
Mann, Steven A. ; Lopez-Beltran, Antonio ; Massari, Francesco ; Pili, Roberto ; Fiorentino, Michelangelo ; Koch, Michael ; Kaimakliotis, Hristos ; Wang, Lisha ; Scarpelli, Marina ; Ciccarese, Chiara ; Moch, Holger ; Montironi, Rodolfo ; Cheng, Liang. / Targeting the programmed cell death-1 pathway in genitourinary tumors : Current progress and future perspectives. In: Current Drug Metabolism. 2017 ; Vol. 18, No. 8. pp. 700-711.
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AU - Fiorentino, Michelangelo

AU - Koch, Michael

AU - Kaimakliotis, Hristos

AU - Wang, Lisha

AU - Scarpelli, Marina

AU - Ciccarese, Chiara

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