Expression of programmed death ligand-1 (PD-L1) in metastatic and postchemotherapy viable testicular germ cell tumors

Copyright © 2021 Elsevier Inc. All rights reserved..

INTRODUCTION: Chemotherapy for testicular germ cell tumors (GCT) is highly effective, with few patients who do not respond. Clinical studies to evaluated novel treatments are challenging given the rarity of these patients. Therefore, we sought to evaluate PD-L1 staining on metastatic and postchemotherapy viable testicular GCTs as a surrogate for potential benefit for immunotherapy targeting the PD-1/PD-L1 axis.

METHODS: Ethics research committee approval for this retrospective study was obtained by four participating institutions (CHU de Québec, St. Joseph's Health Care, Halifax Health Science Centre, Johannes Gutenberg University). Patients with viable metastatic testicular GCTs pathology samples were included. Patients with pure teratoma were excluded. PD-L1 staining with the 22C3 clone was evaluated on samples with >100 viable tumor cells using the combined positive score (CPS).

RESULTS: From 51 patients identified at participating institutions, 24 postchemotherapy and 18 chemotherapy-naive metastatic samples were available for PD-L1 staining, with 9 matched prechemotherapy samples and 7 matched orchiectomy pathology samples, respectively. The median CPS score was 55.6 (IQR 16-100) for all metastatic samples, 44.9 (IQR 13-100) for postchemotherapy metastatic samples, and 68.8 (IQR 38-100) for chemotherapy-naïve metastatic samples, with the median number of viable tumor cells at 545, 500, and 550, respectively. Differences were not significant between chemotherapy-naïve and postchemotherapy samples (P = 0.07), though among non-seminoma GCT metastatic samples, CPS scores were significantly lower postchemotherapy (P = 0.02). Significant differences among postchemotherapy metastatic tumors were also seen according to predominant subtype, with lower CPS scores for predominant yolk sac and higher values for predominant seminoma and choriocarcinoma. In 7 patients with matched specimens pre- and postchemotherapy, a significant increase in CPS was observed for seminoma (26.7 vs. 81.7, P = 0.045), but not nonseminoma GCTs. Comparing all chemotherapy naïve-samples, PD-L1 expression was higher in metastatic samples versus testicular samples (mean CPS 68.8 vs. 39.8, P = 0.02). This was also seen in matched chemotherapy-naïve samples (mean CPS 77.9 vs. 33.1, P = 0.01).

CONCLUSION: Our results suggest that most patients with refractory GCTs postchemotherapy will not benefit from PD-1/PD-L1 immunotherapy. However, the high PD-L1 expression in patients with predominant or pure seminoma post-chemotherapy suggests this may represent a subgroup for whom further trials may be considered.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:39

Enthalten in:

Urologic oncology - 39(2021), 5 vom: 15. Mai, Seite 303.e1-303.e8

Sprache:

Englisch

Beteiligte Personen:

Al-Hogbani, Mofarej [VerfasserIn]
Duguay, Jérémie [VerfasserIn]
Wagner, Daniel-Christoph [VerfasserIn]
Haferkamp, Axel [VerfasserIn]
Joubert, Philippe [VerfasserIn]
Frees, Sebastian [VerfasserIn]
Rendon, Ricardo [VerfasserIn]
Power, Nicholas [VerfasserIn]
Périgny, Martine [VerfasserIn]
Toren, Paul [VerfasserIn]

Links:

Volltext

Themen:

B7-H1 Antigen
CD274 protein, human
Chemotherapy
Germ cell tumor
Immunohistochemistry
Journal Article
Programmed death ligand 1
Research Support, Non-U.S. Gov't
Testis cancer

Anmerkungen:

Date Completed 07.12.2021

Date Revised 14.12.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.urolonc.2021.02.014

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM322429854