Expression of Programmed Death Ligand 1 in Penile Cancer is of Prognostic Value and Associated with HPV Status

Ottenhof, Sarah R.; Djajadiningrat, Rosa S.; Jong, Jeroen de; Thygesen, Helene; Jordanova, Ekaterina S.

doi:10.1016/j.juro.2016.09.088

Cited by 84 publications

(67 citation statements)

References 28 publications

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“…Apart from PD-L1 expression, the presence of tumor-aligned T cells has also been described as predictor of response to immune checkpoint blockade therapy [34]. As > 40% of both tumor and stromal immune cells show a CD8 positivity in penile SCC, a response to immune therapy remains conceivable [31]. At present, there are several ongoing clinical trials using checkpoint inhibitors in penile cancers.…”

Section: Discussionmentioning

confidence: 99%

No Evidence of Microsatellite Instability and Loss of Mismatch-Repair-Protein Expression in Squamous Cell Carcinoma of the Penis

et al. 2019

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Objective: Microsatellite instability (MSI) and a defective mismatch repair (MMR) system were described as beneficial tumor features for response to immune checkpoint therapy (PD-1 blockade). Meanwhile, the FDA approved PD-1/PD-L1 inhibition treatment for any solid tumor showing MSI and/or defects in the MMR system. For squamous cell carcinoma (SCC) of the penis, no data on the frequency of MSI and altered MMR protein expression are available to date. Therefore, we investigated the MSI status and the expression of MMR proteins in a large cohort of penile SCCs. Methods: The MSI status of 105 archival formalin-fixed, paraffin-embedded penile SCCs was analyzed using the 5 markers of the NCI consensus panel for MIS testing (BAT25, 26, D2S123, D17S250, and D5S346), or, in cases without representative nontumorous tissue using a validated panel of 5 quasimonomorphic mononucleotide repeat markers (BAT 25, 26 and NR21, 24, 27). The expression of the MMR proteins MLH1, MSH2, MSH6, and PMS2 was analyzed using immunohistochemistry and a tissue microarray of a subset of penile SCCs from our cohort (n = 75). Results: Overall, in 96/105 cases, at least 4 microsatellite markers gave interpretable results. None of the cases showed MSI. Immunohistochemistry for MMR proteins was analyzable in 70/75 cases. All cases showed a regular expression of the MMR proteins. Conclusion: MSI and defects in MMR protein expression are not regular features of penile SCC and might not act as biomarkers for PD-1/PD-L1 blockade therapy in penile carcinoma.

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Section: Discussionmentioning

confidence: 99%

No Evidence of Microsatellite Instability and Loss of Mismatch-Repair-Protein Expression in Squamous Cell Carcinoma of the Penis

et al. 2019

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“…Recently, Ottenhof et al 34 published an article discussing the relationship between HPV status and PD-L1 expression, and they reported that high risk HPV-negative patients tend to have positive PD-L1 expression in tumor cells. However, although it has been reported that HPV DNA can be detected in approximately half of penile cancers, the prevalence of HPV infection in penile cancer patients from Asia is relatively low with only 13.4%.…”

Section: Discussionmentioning

confidence: 99%

Tumor PD-L1 expression is correlated with increased TILs and poor prognosis in penile squamous cell carcinoma

Deng

Guo

et al. 2017

OncoImmunology

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Despite its rare incidence worldwide, penile squamous cell carcinoma (PeSCC) still presents with significant morbidity and mortality due to the limited treatment options for advanced patients, especially those in developing countries. The program death-1 (PD-1)/PD-1 ligand (PD-L1) axis has been demonstrated to play an important role in tumor immune escape, and immunotherapies targeting this pathway have shown great success in certain cancer types. Here, we analyzed the expression pattern of PD-L1 in tumor cells and tumorinfiltrating lymphocytes (TILs) in PeSCC with a multi-center cohort. We found that the majority of PeSCCs (53.4%) were PD-L1-positive and that high PD-L1 expression in tumor cells was associated with a poor prognosis. Notably, PD-L1 expression in tumor cells was significantly associated with the extent of TILs and CD8 C TILs. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) showed that PD-L1 was positively correlated with interferon-gamma (IFNg) and CD8 C gene expression. Moreover, we defined the constitutive and inducible surface expression of PD-L1 in newly established primary PeSCC cell lines. Interestingly, two PeSCC cell lines had high intrinsic PD-L1 expression. Another cell line showed low PD-L1 expression, but the PD-L1 expression could be induced by IFNg stimulation. Overall, our data showed that high PD-L1 expression in penile tumor cells indicated a poor prognosis. The upregulation of PD-L1 in PeSCC included both extrinsic and intrinsic mechanisms. These findings indicated that the PD-1/PD-L1 axis might be a potential therapeutic target for patients with penile squamous cell carcinoma.

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“…This was facilitated by PD-L1 + tumor and immune cells, and could be prevented by anti-PD-1/PD-L1 immunotherapy. 11 A recent study demonstrated that PD-L1 was a solid biomarker of productive HPV infection of the cervix, and that it was significantly upregulated in both cancer and surrounding inflammatory cells in cervical cancer compared to other gynecologic malignancies. 12 In a previous study, we examined the expression of PD-1 and PD-L1 on cervical Tcells and dendritic cells (DC), respectively, from HR-HPV(À) or HR-HPV(+) women with different CIN grades.…”

Section: Introductionmentioning

confidence: 99%

Expressions of programmed death (PD)‐1 and PD‐1 ligand (PD‐L1) in cervical intraepithelial neoplasia and cervical squamous cell carcinomas are of prognostic value and associated with human papillomavirus status

Yang

et al. 2017

J of Obstet and Gynaecol

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Expression of Programmed Death Ligand 1 in Penile Cancer is of Prognostic Value and Associated with HPV Status

Abstract: PD-L1 was expressed in 48% of penile carcinomas and mainly in high risk HPV negative tumors. The pattern of expression was a prognostic factor as marginal expression was associated with absent lymph node metastases and diffuse expression was associated with poor survival.

Cited by 84 publications

References 28 publications

No Evidence of Microsatellite Instability and Loss of Mismatch-Repair-Protein Expression in Squamous Cell Carcinoma of the Penis

No Evidence of Microsatellite Instability and Loss of Mismatch-Repair-Protein Expression in Squamous Cell Carcinoma of the Penis

Tumor PD-L1 expression is correlated with increased TILs and poor prognosis in penile squamous cell carcinoma

Expressions of programmed death (PD)‐1 and PD‐1 ligand (PD‐L1) in cervical intraepithelial neoplasia and cervical squamous cell carcinomas are of prognostic value and associated with human papillomavirus status

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