Immunotherapy for urothelial cancer: from the diagnostic pathologist’s point of view

Figures & data

Figure 1. PD-L1 expression in invasive high-grade urothelial carcinoma. Strong and diffuse membranous expression is seen in the epithelial cells (Right) whereas it is mostly cytoplasmic in the tumor-infiltrating immune cells (left) (PD-L1 IHC 22C3 pharmDx by Dako/Agilent).

Table 1. Diagnostic PD-L1 expression assay evaluation for bladder cancer.

Companion diagnostic assay (Manufacturer)	PD- protein expression evaluation (Algorithm)	IO-Drug Trials
SP263 (Ventana)	assessed with the immune cells (IC)/tumor cells (TC) algorithm and considered positive if ≥25% TCs or ICs are immunoreactive^5	Durvalumab NCT01693562
SP142 (Ventana)	staining is scored with the IC score and recorded as positive when the positive ICs represented ≥5% of the TC area^6	Atezolizumab IMvigor 210 trial IMvigor 211 ABACUS trial
22C3 (Dako)	assessed with the combined positive score (CPS) and considered positive when the CPS-score is ≥10%^7. CPS is calculated by combining the positive TC and IC staining and expressing it relative to the total TCs^7	Pembrolizumab KEYNOTE-052 KEYNOTE-045 PURE-01 trial KEYNOTE-057

Figure 2. Complex interplay of chemokines and cytokines classify the inflammatory state of the tumor microenvironment. Interferon-g (IFN-g) released by activated T cells and NK cells activates STAT1, IDO-1 (indolamine oxygenase I) and CMKLR1 in dendritic cells and macrophages (1). STAT-1 mediated signaling and additional pathways produce the chemokines CCL5 and CXCL9 (2). This recruits additional T cells into the tumor microenviroment through CXCR6. IFN-g stimulates the expression of HLA molecules and proteasome components including PSMB10 (3). Finally, IFN-g upregulates a number of immune checkpoint molecules including PD-L1, PD-L2, TIGIT, LAG-3, and B7-H3 on T cells (4). Reproduced under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/) – Figure 4a Ref [18]. J Immunother Cancer. 2017; 5:94.

Aggen DH, Drake CG. Biomarkers for immunotherapy in bladder cancer: a moving target. J Immunother Cancer. 2017;5(1):94.

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