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XIST-Promoter Demethylation as Tissue Biomarker for Testicular Germ Cell Tumors and Spermatogenesis Quality
Open AccessFeature PaperArticle

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

1
Department of Pathology, Portuguese Oncology Institute of Porto (IPOP), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
2
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
3
Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-513 Porto, Portugal
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Department of Medical Oncology & Urology Clinic, Portuguese Oncology Institute of Porto (IPOP), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
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Department of Urology & Urology Clinic, Portuguese Oncology Institute of Porto (IPOP), R. Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
*
Authors to whom correspondence should be addressed.
Joint senior authors.
Cancers 2019, 11(10), 1535; https://doi.org/10.3390/cancers11101535
Received: 13 August 2019 / Revised: 28 September 2019 / Accepted: 8 October 2019 / Published: 11 October 2019
(This article belongs to the Special Issue Benign and Malignant Germ Cell Tumors)
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. View Full-Text
Keywords: CTLA-4; immune checkpoints; mismatch repair; PD-L1; prognosis; survival; testicular germ cell tumors CTLA-4; immune checkpoints; mismatch repair; PD-L1; prognosis; survival; testicular germ cell tumors
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MDPI and ACS Style

Lobo, J.; Rodrigues, Â.; Guimarães, R.; Cantante, M.; Lopes, P.; Maurício, J.; Oliveira, J.; Jerónimo, C.; Henrique, R. 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. Cancers 2019, 11, 1535.

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