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Cited by 69Cancer Immunotherapy and BiomarkersTesticular diseases and treatmentsImmunotherapy and Immune Responses

Detailed Characterization of Immune Cell Infiltrate and Expression of Immune Checkpoint Molecules PD-L1/CTLA-4 and MMR Proteins in Testicular Germ Cell Tumors Disclose Novel Disease Biomarkers

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Lobo, João, Rodrigues, Ângelo, Guimarães, Rita, Cantante, Mariana, Lopes, Paula, Maurício, Joaquina, Oliveira, Jorge, Jerónimo, Carmen +1 more·2019·Cancers
DOI 10.3390/cancers11101535PMC PMC6826711
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Abstract

Background: The immune infiltrate plays an important part in testicular germ cell tumors, but it remains scarcely studied. We aimed at thoroughly characterizing the immune infiltrate and expression of immune checkpoints PD-L1/CTLA-4 and mismatch repair (MMR) proteins in these neoplasms, seeking for associations with patient outcome. Methods: A total of 162 consecutively diagnosed patients (2005–2018) were included. Immunostaining for PD-L1, CTLA-4 and MMR proteins was independently assessed both in immune cells (ICs) and tumor cells (TCs) of primary tumors and metastases, and characterization of IC populations was pursued. Results: PD-L1 and CTLA-4 positivity in ICs was frequent (85.5% and 96.3%). Patients with absent PD-L1 positive ICs exhibited significantly worse relapse-free survival (hazard ratio = 4.481, 95% CI 1.366–14.697, p = 0.013), both in univariable and multivariable analysis. Lower CD20 and CD3 IC infiltration in seminomas associated with higher disease stage (p = 0.0216, p = 0.0291). CTLA-4 TC intensity was significantly higher in yolk sac tumor, choriocarcinoma and teratoma, while PD-L1 TC positivity was significantly more frequent in choriocarcinoma. Both PD-L1 and CTLA-4 immunoexpression in ICs of metastatic samples was frequent (100% and 88.2%). MMR proteins were differentially expressed among the different tumor subtypes. Conclusions: Immune infiltrate/checkpoints associate with patients’ outcome, constituting novel (potentially targetable) disease biomarkers.

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Authors
Lobo, J., Rodrigues, Â., Guimarães, R., Cantante, M., Lopes, P., Maurício, J., Oliveira, J., Jerónimo, C., & Henrique, R.
Affiliations
  • Universidade do Porto (PT)
  • IPO Porto (PT)
  • Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (GEBC CI-IPOP) and Porto Comprehensive Cancer Center (P.CCC), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
Corresponding author
Henrique, Rui
ORCID
Venue
Cancers
Publisher
MDPI AG
Published
2019-10-11
Volume
11
Issue
10
Pages
1535
ISSN
2072-6694 (ISSN-L)
DOI
10.3390/cancers11101535
PMC
PMC6826711
OpenAlex
W2979880332
Cited by
69
References
5
Citations by year
2026: 4 · 2025: 7 · 2024: 13 · 2023: 13 · 2022: 7 · 2021: 14 · 2020: 11
FWCI
3.34
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
Fundação para a Ciência e a Tecnologia (PTDC/MECONC/ 29043/2017, SFRH/BD/132751/2017)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Surgery › Testicular diseases and treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
testicular germ cell tumors, immune cell infiltration, PD-L1, CTLA-4, mismatch repair proteins, immune checkpoint, tumor microenvironment, disease biomarkers, seminoma, yolk sac tumor, choriocarcinoma, teratoma, metastasis, relapse-free survival, CD20, CD3

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