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Cited by 27Cancer Immunotherapy and BiomarkersTesticular diseases and treatmentsAngiogenesis and VEGF in Cancer

Increased tumor vascularization is associated with the amount of immune competent PD‑1 positive cells in testicular germ cell tumors

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Jennewein, Lukas, Bartsch, Georg, Gust, Kilian, Kvasnicka, Hans‑Michael, Haferkamp, Axel, Blaheta, Roman, Mittelbronn, Michel, Harter, Patrick +1 more·2018·Oncology Letters
DOI 10.3892/ol.2018.8597PMC PMC6004709
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Abstract

Testicular germ cell cancer in a metastatic state is curable with a cisplatin-based first line chemotherapy. However, 10-15% of these patients are resistant to first line chemotherapy and are thus left with only palliative options. Immunotherapies and inhibition of angiogenesis used in multiple types of cancer; however, the molecular context of angiogenesis and immune checkpoints in the development and progression of testicular cancers is still unknown. Therefore, the present study performed tissue micro array based analysis of 84 patients with immunohistochemistry of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1) and vascular endothelial growth factor receptor 2 (VEGFR2) of testicular cancer and corresponding normal appearing testis tissue, matching the results with clinical data. The results demonstrated that PD-L1 was significantly upregulated in testicular tumors and that PD-1 positive cells significantly infiltrated the testicular tumor when compared with normal testicular tissue. VEGFR2 was significantly upregulated in testicular cancer. It was indicated that PD-1 expressing cytotoxic cells may require pathologic tumor vessels to pass the blood-testis-barrier in order to migrate into the tumor. Notably, when matching the clinical data for PD-1, PD-L1 and VEGFR2 there were no differences in expression in the different International Germ Cell Cancer Collaborative Group stages of non-seminoma. These data suggested that the anti-PD-1/PD-L1 immunotherapy and the anti-angiogenic therapy, sequentially or in combination, may be a promising option in the treatment of testicular cancer.

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  • Peri-tumoral migration of PD-1-positive infiltrating cells in testicular tissue containing GCN is facilitated by angiogenic signaling through the VEGFR2 receptor.

    “Peri-tumoral migration of these PD-1-positive infiltrating cells in testicular tissue containing GCN is facilitated by angiogenic signaling through the VEGFR2 receptor [25].”

    From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [25]

    The Discussion (page not provided) hypothesizes that PD-1-positive immune cells migrate into testicular tumors through abnormal vessels and an impaired blood-testis barrier. The Results report higher VEGFR2 staining in tumors, particularly in areas with greater vessel density, but the paper does not establish that VEGFR2 signaling facilitates cell migration or examine peri-tumoral migration specifically in tissue containing GCN. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Microarray-based analyses revealed abundance of PD-1-positive tumor infiltrating T cells (TILs).

    “Besides PD-L1 overexpression in testicular tumor cells, microarray-based analyses revealed the abundance of PD-1-positive tumor infiltrating T cells, also known as TILs.”

    From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [25]

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Cited by

Sorted by citations

Authors
Jennewein, L., Bartsch, G., Gust, K., Kvasnicka, H., Haferkamp, A., Blaheta, R., Mittelbronn, M., Harter, P., & Mani, J.
Affiliations
  • Goethe University Frankfurt (DE)
  • Johannes Gutenberg University Mainz (DE)
  • Medical University of Vienna (AT)
  • Centre Hospitalier de Luxembourg (LU)
Corresponding author
Mani, Jens
ORCID
Venue
Oncology Letters
Publisher
Spandidos Publications
Published
2018-04-27
Volume
15
Issue
6
Pages
9852-9860
ISSN
  • 1792-1074 (ISSN-L)
  • 1792-1082
DOI
10.3892/ol.2018.8597
PMC
PMC6004709
OpenAlex
W2799985236
Cited by
27
References
5
Citations by year
2026: 1 · 2025: 4 · 2024: 7 · 2023: 2 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2
FWCI
0.85
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Oncology Letters (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nc-nd)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Surgery › Testicular diseases and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
Keywords
testicular germ cell tumors, PD-1, PD-L1, VEGFR2, tumor angiogenesis, tumor vascularization, immune checkpoint, cytotoxic T lymphocytes, blood-testis barrier, non-seminoma, anti-PD-1 therapy, anti-angiogenic therapy, chemoresistance

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