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Cited by 16Cancer Immunotherapy and BiomarkersInflammatory Biomarkers in Disease PrognosisTesticular diseases and treatments

Combined Assessment of Immune Checkpoint Regulator VISTA on Tumor-Associated Immune Cells and Platelet-to-Lymphocyte Ratio Identifies Advanced Germ Cell Tumors with Higher Risk of Unfavorable Outcomes

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Pęksa, Rafał, Kunc, Michał, Popęda, Marta, Piątek, Michał, Bieńkowski, Michał, Żok, Jolanta, Starzyńska, Anna, Perdyan, Adrian +3 more·2021·Cancers
DOI 10.3390/cancers13081750PMC PMC8067539
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Abstract

In the current study, we aimed to investigate whether expression of immune checkpoint proteins (V-domain Ig suppressor of T cell activation (VISTA) and programmed death-ligand 1 (PD-L1)) and markers of systemic inflammation could predict progression/relapse and death in the cohort of 180 patients with testicular germ-cell tumors (GCTs). Expression of PD-L1 and VISTA was assessed by immunohistochemistry utilizing tissue microarrays. To estimate systemic inflammation neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) were calculated. We found high PD-L1 and VISTA expression on tumor-associated immune cells (TAICs) in 89 (49.44%) and 63 (37.22%) of GCTs, respectively, whereas tumor cells besides trophoblastic elements were almost uniformly negative. High PD-L1 was associated with seminomatous histology and lower stage. Relapses in stage I patients occurred predominantly in cases with low numbers of PD-L1 and VISTA-expressing TAICs. In stage II/III disease, the combination of low VISTA-expressing TAICs and high PLR was identified as predictor of shorter event-free survival (HR 4.10; 1.48–11.36, p = 0.006) and overall survival (HR 15.56, 95% CI 1.78–135.51, p = 0.001) independently of tumor histology and location of metastases. We demonstrated that the assessment of immune checkpoint proteins on TAICs may serve as a valuable prognostic factor in patients with high-risk testicular GCTs. Further study is warranted to explore the predictive utility of these biomarkers in GCTs.

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  • 3.6% of men with non-seminomatous embryonal tumors had complete absence of PD-L1.

    “Conversely, a small percentage of seminoma patients (7.2%) had complete absence of PD-L1, as did 3.6% of men with non-seminomatous embryonal (NSE) tumors.”

    From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [28]

    Results §3.1 reports complete absence of PD-L1 in three mixed germ cell tumors, representing 3.6% of nonseminomas. It does not identify those three tumors as embryonal tumors, so the percentage and absence of PD-L1 are supported but the embryonal designation is not. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Mixed tumors, teratomas or areas containing teratomas displayed very weak or no expression of immune checkpoints, with PD-L1 levels below 5% and VISTA cell positivity below 5%.

    “Mixed tumors, teratomas or areas containing teratomas displayed very weak or no expression of immune checkpoints, with PD-L1 levels below 5% and VISTA cell positivity below 5% [28].”

    From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [28]

    The Results (§3.1) report very weak or absent checkpoint expression in pure teratomas and teratoma areas of mixed tumors, with a PD-L1 histoscore below 5 and fewer than 5% VISTA-positive cells. The claim extends this finding to mixed tumors generally and describes the PD-L1 histoscore as a percentage; neither is supported by the passage. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Low VISTA expression in tumor-associated immune cells is associated with shorter progression-free and overall survival.

    “Low VISTA expression in tumor-associated immune cells was associated with shorter progression-free and overall survival [28].”

    From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [28]

    The Results (§3.3.3; page unavailable) associate low VISTA with more events and deaths in stage II/III germ-cell tumors, but the reported p-values (0.1031 and 0.054) indicate trends rather than statistically significant findings. The stronger survival result applies to low VISTA combined with high platelet-to-lymphocyte ratio; the paper reports event-free survival, not specifically progression-free survival. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Combined PD-L1 and VISTA overexpression is particularly found in patients with choriocarcinoma components.

    “Combined PD-L1 and VISTA overexpression is particularly found in patients with choriocarcinoma components.”

    From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [28]

  • 37.22% of patients exhibited high VISTA expression.

    “Notably, 37.22% of patients exhibited high VISTA expression, while 49.44% showed high PD-L1 expression in a recent study.”

    From The Immune Landscape and Immunotherapeutic Strategies in Platinum-Refractory Testicular Germ Cell Tumors (2024) · cites this paper as [28]

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Authors
Pęksa, R., Kunc, M., Popęda, M., Piątek, M., Bieńkowski, M., Żok, J., Starzyńska, A., Perdyan, A., Sowa, M., Duchnowska, R., & Biernat, W.
Affiliations
  • Gdańsk Medical University (PL)
  • Wojewódzki Szpital Specjalistyczny nr 5 im. św. Barbary w Sosnowcu (PL)
  • Department of Oncology, Regional Oncology Center in Gdansk, 80219 Gdansk, Poland
  • Wojskowy Instytut Medyczny (PL)
Corresponding author
Pęksa, Rafał
ORCID
Venue
Cancers
Publisher
MDPI AG
Published
2021-04-07
Volume
13
Issue
8
Pages
1750
ISSN
2072-6694 (ISSN-L)
DOI
10.3390/cancers13081750
PMC
PMC8067539
OpenAlex
W3140105995
Cited by
16
References
5
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 6 · 2021: 2
FWCI
1.37
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancers (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Gdański Uniwersytet Medyczny (01-0395/08/643)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
  • Health Sciences › Medicine › Surgery › Testicular diseases and treatments
Keywords
VISTA, PD-L1, testicular germ cell tumors, immune checkpoint molecules, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic inflammation, tumor-infiltrating immune cells, prognostic factors, event-free survival, overall survival, tumor recurrence, seminoma

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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