Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor infiltrating lymphocytes in testicular germ cell tumors
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// Michal Chovanec 1, 2, 7, * , Zuzana Cierna 3, * , Viera Miskovska 4 , Katarina Machalekova 5 , Daniela Svetlovska 2, 6 , Katarina Kalavska 2, 7, 8 , Katarina Rejlekova 1, 7 , Stanislav Spanik 4 , Karol Kajo 5 , Pavel Babal 3, 9 , Jozef Mardiak 1, 7 , Michal Mego 1, 2, 7 1 2nd Department of Oncology, Comenius University, Faculty of Medicine & National Cancer Institute, Bratislava, Slovak Republic 2 Translational Research Unit, 2nd Department of Oncology, Comenius University, Faculty of Medicine & National Cancer Institute, Bratislava, Slovak Republic 3 Department of Pathology, Comenius University, Faculty of Medicine, Bratislava, Slovak Republic 4 1st Department of Oncology, Comenius University, Faculty of Medicine & St. Elisabeth Cancer Institute, Bratislava, Slovak Republic 5 Department of Pathology, Slovak Medical University St. Elisabeth Cancer Institute, Bratislava, Slovak Republic 6 Department of Clinical Trials, National Cancer Institute, Bratislava, Slovak Republic 7 Department of Medical Oncology, National Cancer Institute, Bratislava, Slovak Republic 8 Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Slovak Republic 9 Faculty Hospital with Policlinics Skalica, a.s., Skalica, Slovak Republic * M-CH and Z-C share the first authorship Correspondence to: Michal Mego, email: misomego@gmail.com Keywords: programmed death-ligand 1, programmed cell death protein 1, tumor infiltrating lymphocytes, prognostic factor, testicular germ cell tumors Received: August 12, 2016 Accepted: January 10, 2017 Published: February 21, 2017 ABSTRACT Purpose: Testicular germ cell tumors (TGCTs) are nearly universally curable malignancies. Nevertheless, standard cisplatin-based chemotherapy is not curative in a small subgroup of patients. Previously, we showed that PD-L1 overexpression is associated with worse prognosis in TGCTs, while tumor infiltrating lymphocytes (TILs) are prognostic in different types of cancer. This study aimed to evaluate the prognostic value of PD-1 and PD-L1 expressing TILs in TGCTs. Results: PD-L1 positive TILs were found significantly more often in seminomas (95.9% of patients) and embryonal carcinomas (91.0%) compared to yolk sac tumors (60.0%), choriocarcinomas (54.5%) or teratomas (35.7%) (All p < 0.05). TGCTs patients with high infiltration of PD-L1 positive TILs (HS ≥ 160) had significantly better progression-free survival (HR = 0.17, 95% CI 0.09 – 0.31, p = 0.0006) and overall survival (HR = 0.08, 95% CI 0.04 – 0.16, p = 0.001) opposite to patients with lower expression of PD-L1 (HS < 150). PD-1 expressing TILs were not prognostic in TGCTs. Materials and Methods: Surgical specimens from 240 patients with primary TGCTs were included into this translational study. The PD-1 and PD-L1 expression on tumor and TILs were detected by immunohistochemistry using anti-PD-1 and anti-PD-L1 monoclonal antibody. Scoring was performed semiquantitatively by weighted histoscore (HS) method. Conclusions: The prognostic value of PD-L1 expressing TILs in TGCTs was demonstrated for the first time.
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Patients with GCN and abundant PD-L1(+) TILs in the TME had significantly better outcomes than patients with lower expression.
“In this context, a study by Chovanec et al. revealed that patients with GCN and abundant PD-L1 (+) TILs in the TME had significantly better outcomes than patients with lower expression [26].”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [26]
The Results report significantly better progression-free and overall survival among patients with primary testicular germ cell tumors whose TILs had high PD-L1 expression. The claim says “patients with GCN,” which is broader than the population studied; the finding is supported for primary testicular germ cell tumors, not GCN generally. (LLM, conf=0.86)
Experimental — accuracy not yet measuredDecreased PD-L1 expression in TILs is associated with high-risk disease as defined by IGCCCG.
“The notion that the ability of testicular cancer cells to escape the immune system leading to disease dissemination is linked to reduced PD-L1 expression on TILs is further supported by a notable association between decreased PD-L1 expression in TILs and the presence of high-risk disease as defined by the International Germ Cell Cancer Collaborative Group (IGCCCG) [26].”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [26]
The ability of testicular cancer cells to escape the immune system leading to disease dissemination is linked to reduced PD-L1 expression on TILs.
“The notion that the ability of testicular cancer cells to escape the immune system leading to disease dissemination is linked to reduced PD-L1 expression on TILs is further supported by a notable association between decreased PD-L1 expression in TILs and the presence of high-risk disease as defined by the International Germ Cell Cancer Collaborative Group (IGCCCG) [26].”
From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [26]
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Self-citation
- Authors
- Chovanec, M., Cierna, Z., Miskovska, V., Machalekova, K., Svetlovska, D., Kalavska, K., Rejlekova, K., Spanik, S., Kajo, K., Babal, P., Mardiak, J., & Mego, M.
- Affiliations
- Comenius University Bratislava (SK)
- Department of Pathology, Comenius University, Faculty of Medicine, Bratislava, Slovak Republic
- Department of Pathology, Slovak Medical University St. Elisabeth Cancer Institute, Bratislava, Slovak Republic
- Translational Research Unit, 2nd Department of Oncology, Comenius University, Faculty of Medicine & National Cancer Institute, Bratislava, Slovak Republic
- 2nd Department of Oncology, Comenius University, Faculty of Medicine & National Cancer Institute, Bratislava, Slovak Republic
- Slovak Medical University (SK)
- Corresponding author
- Chovanec, Michal
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2017-02-21
- Volume
- 8
- Issue
- 13
- Pages
- 21794-21805
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC5400624
- OpenAlex
- W2589245300
- Cited by
- 79
- References
- 40
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 10 · 2023: 9 · 2022: 9 · 2021: 4 · 2020: 16 · 2019: 9 · 2018: 12 · 2017: 2
- FWCI
- 4.70
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Surgery › Testicular diseases and treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Lymphoma Diagnosis and Treatment
- Keywords
- PD-L1, tumor-infiltrating lymphocytes, testicular germ cell tumors, prognostic factors, PD-1, PD-L1 expression, cisplatin resistance, cisplatin-based chemotherapy, tumor immune microenvironment, tumor-infiltrating macrophages, tumor-infiltrating neutrophils, tumor-infiltrating T cells, tumor-infiltrating B cells, tumor-infiltrating dendritic cells, tumor-infiltrating NK cells, tumor-infiltrating Treg cells, tumor-infiltrating myeloid cells
- MeSH terms
- Adolescent, Adult, Aged, Humans, Immunohistochemistry, Male, Middle Aged, Neoplasms, Germ Cell and Embryonal, Prognosis, Testicular Neoplasms, Biomarkers, Tumor, Proportional Hazards Models, Lymphocytes, Tumor-Infiltrating, Disease-Free Survival, Tissue Array Analysis, Kaplan-Meier Estimate, Young Adult, B7-H1 Antigen, Programmed Cell Death 1 Receptor
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