Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor infiltrating lymphocytes in testicular germ cell tumors

Abstract Objectives To characterize the tumor microenvironment of testicular germ cell tumors (GCTs) using immunohistochemical markers. Methods Seventy-seven orchiectomies, including 36 nonmetastatic (NM) seminomas, 15 metastatic (M) seminomas, 13 nonmetastatic nonseminomatous germ cell tumors (NSGCTs), and 13 metastatic NSGCTs, were studied with PD-1, PD-L1, FOXP3, CD68, CD163, and mismatch repair (MMR) immunohistochemistry. FOXP3+ and PD-1+ tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) expressing CD68 and CD163 were enumerated. PDL-1 expression was evaluated on tumor cells and macrophages. Results GCTs primarily express PD-L1 on TAMs, except choriocarcinoma, where true tumor cell positivity was noted. Seminomas reveal increased intratumoral PD-L1+ TAMs compared with NSGCTs (P < .05). Activated TILs are increased in NM-seminomas compared with M-seminomas (P < .05). All GCTs retained MMR expression. Conclusions Robust PD-L1+ TAMs are significantly expanded in seminomas compared with NSGCTs. Among all GCTs, only choriocarcinoma cells reveal true positivity for PD-L1. These findings expand the realm of potentially targeted treatments for GCTs.

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Systemic immune-inflammation index is prognostic in testicular germ cell tumors with PD-L1 expressing tumor infiltrating lymphocytes.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e16042 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e16042-e16042 ◽

Cited By ~ 3

Author(s):

Michal Chovanec ◽

Zuzana Cierna ◽

Vera Miskovska ◽

Katarina Machalekova ◽

Katarina Kalavska ◽

...

Keyword(s):

Germ Cell ◽

Prognostic Value ◽

Germ Cell Tumors ◽

Tumor Infiltrating Lymphocytes ◽

Collaborative Group ◽

Testicular Germ Cell Tumors ◽

Testicular Germ Cell ◽

Immune Inflammation ◽

Validation Set ◽

Infiltrating Lymphocytes

e16042 Background: Systemic immune-inflammation index (SII) and programmed death-ligand 1 (PD-L1) are prognostic in various types of malignancies. Recently we have shown a prognostic value of PD-L1 expression on tumor cells and tumor infiltrating lymphocytes (TILs) in testicular germ cell tumors (GCT). This study aimed to evaluate prognostic role of SII in a GCT population of patients expressing PD-L1 on TILs. Methods: SII was calculated using platelet (P), neutrophil (N) and lymphocyte (L) counts measured prior to chemotherapy (SII = P x N/L). SII was calculated in our discovery set of 216 patients with GCT treated at National Cancer Institute and St. Elisabeths' Cancer Institute between 1999 and 2015. A model with median obtained from the discovery data was tested in an independent validation set of 181 patients that were included in a retrospective study evaluating PD-L1 on TILs in GCT. PD-L1 on TILs was detected by immunohistochemistry and scored semiquantitatively by weighted histoscore method. SII was dichotomized into low and high categories based on median value. Results: Low SII ( < 1003) was found in 133 patients (73.5%) as opposed to 48 patients (26.5%) with high SII (≥ 1003). Ten (5.5%) and 171 patients (94.5%) from the validaton set had low (HS < 150) and high (HS ≥ 160) expression of PD-L1 on TILs, respectively. Discovery group of patients with high SII had significantly shorter PFS (HR = 4.48, 95% CI 2.44 – 8.23, p = 0.0000) and OS (HR = 6.10 95% CI 3.11 – 11.95, p = 0.0000) opposite to patients with low SII. PFS from validation set confirmed shorter PFS (HR = 3.03, 95% CI 3.86 – 7.46, p = 0.0062) and OS (HR = 6.49 95% CI 2.10 – 20.03, p = 0.0001) in patients with high versus low SII. A combined prognostic value of PD-L1 TILs and SII uncovered three prognostic groups. The best prognosis was observed in patients with low SII and high PD-L1 on TILs, the worst prognosis was seen in patients with high SII and low PD-L1 on TILs. Patients with SII and PD-L1 on TILs both values high or low had intermediate prognosis. Conclusions: SII was prognostic in our patients with GCT independently of international germ cell cancer collaborative group criteria, suggesting involvement of immune mechanisms in the behavior of GCT.

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Expression of programmed death ligand-1 (PD-L1) in metastatic and postchemotherapy viable testicular germ cell tumors

Urologic Oncology Seminars and Original Investigations ◽

10.1016/j.urolonc.2021.02.014 ◽

2021 ◽

Author(s):

Mofarej Al-Hogbani ◽

Jérémie Duguay ◽

Daniel-Christoph Wagner ◽

Axel Haferkamp ◽

Philippe Joubert ◽

...

Keyword(s):

Germ Cell ◽

Germ Cell Tumors ◽

Testicular Germ Cell Tumors ◽

Testicular Germ Cell ◽

Programmed Death Ligand 1 ◽

Programmed Death

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Re: Prognostic Value of Programmed-Death-1 Receptor (PD-1) and its Ligand 1 (PD-L1) in Testicular Germ Cell Tumors

The Journal of Urology ◽

10.1016/j.juro.2017.11.041 ◽

2018 ◽

Vol 199 (2) ◽

pp. 344-344

Author(s):

Jerome P. Richie

Keyword(s):

Germ Cell ◽

Prognostic Value ◽

Germ Cell Tumors ◽

Testicular Germ Cell Tumors ◽

Testicular Germ Cell ◽

Programmed Death ◽

Programmed Death 1

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The Role of the Mouse Y Chromosome on Susceptibility to Testicular Germ Cell Tumors

Cancer Research ◽

10.1158/0008-5472.can-08-4881 ◽

2009 ◽

Vol 69 (8) ◽

pp. 3614-3618 ◽

Cited By ~ 5

Author(s):

Philip D. Anderson ◽

Man-Yee Lam ◽

Christophe Poirier ◽

Colin E. Bishop ◽

Joseph H. Nadeau

Keyword(s):

Germ Cell ◽

Y Chromosome ◽

Germ Cell Tumors ◽

Testicular Germ Cell Tumors ◽

Testicular Germ Cell

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The role of paclitaxel in chemosensitive urological malignancies: current strategies in bladder cancer and testicular germ-cell tumors

World Journal of Urology ◽

10.1007/bf00183114 ◽

1996 ◽

Vol 14 (6) ◽

Cited By ~ 9

Author(s):

C. Bokemeyer ◽

J.T. Hartmann ◽

M.A. Kuczyk ◽

M.C. Truss ◽

J. Beyer ◽

...

Keyword(s):

Bladder Cancer ◽

Germ Cell ◽

Germ Cell Tumors ◽

Testicular Germ Cell Tumors ◽

Testicular Germ Cell ◽

Urological Malignancies

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Role of microRNAs in mammalian spermatogenesis and testicular germ cell tumors

Reproduction ◽

10.1530/rep-14-0239 ◽

2015 ◽

Vol 149 (3) ◽

pp. R127-R137 ◽

Cited By ~ 33

Author(s):

Li Wang ◽

Chen Xu

Keyword(s):

Germ Cell ◽

Expression Profiles ◽

Regulation Of Gene Expression ◽

Germ Cell Tumors ◽

Testicular Germ Cell Tumors ◽

Mirna Regulation ◽

Testicular Germ Cell ◽

Complex Process ◽

Regulatory Functions

microRNAs (miRNAs) are a class of small endogenous RNAs, 19–25 nucleotides in size, which play a role in the regulation of gene expression at transcriptional and post-transcriptional levels. Spermatogenesis is a complex process through which spermatogonial stem cells (SSCs) proliferate and differentiate into mature spermatozoa. A large number of miRNAs are abundantly expressed in spermatogenic cells. Growing evidence supports the essential role of miRNA regulation in normal spermatogenesis and male fertility and cumulative research has shown that this form of regulation contributes to the etiology of testicular germ cell tumors (TGCTs). In this review, we addressed recent advancements of miRNA expression profiles in testis and focused on the regulatory functions of miRNA in the process of SSC renewal, spermatogonial mitosis, spermatocyte meiosis, spermiogenesis, and the occurrence of TGCTs.

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