Immunohistochemical status of PD-L1 in thymoma and thymic carcinoma

Katsuya, Yuki; Fujita, Yu; Horinouchi, Hidehito; Ohe, Yuichiro; Watanabe, Shun‐ichi; Tsuta, Koji

doi:10.1016/j.lungcan.2015.03.003

Cited by 158 publications

(148 citation statements)

References 36 publications

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“…The specificity and reproducibility of this antibody have been confirmed in previous studies. [28][29][30] Similar to the previous report, we found that 53.4% of the patient samples showed positive tumor membrane PD-L1 staining, and the higher PD-L1 expression in tumor cells was associated with shorter CSS. However, neither PD-L1 positivity in TILs nor the extent of TILs was correlated with CSS.…”

Section: Discussionsupporting

confidence: 89%

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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Section: Discussionsupporting

confidence: 89%

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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“…Thus far, few studies have examined PD-L1 expression in thymic epithelial tumors (22)(23)(24). Confined to thymic carcinoma as a subset of thymic epithelial tumors, only one of these reports mentioned the prognostic role of PD-L1, finding that there was no difference in OS according to PD-L1 positivity (23).…”

Section: Discussionmentioning

confidence: 99%

“…PD-L1 expression was assessed under 400-fold magnification using an optical microscope in an entire field for each TMA spot and was quantified by the H-score approach, in which the proportion and intensity of tumor cells positive for PD-L1 is determined (23,27). Specifically, the PD-L1 staining intensity of individual tumor cells was graded from 0 to 3 (0, negative; 1, weak; 2, moderate; 3, strong).…”

Section: Appraisal Of Pd-l1 Expressionmentioning

confidence: 99%

“…Indeed, PD-L1 expression and PD-1 þ tumor-infiltrating lymphocyte (TIL) abundance have been reported to be prognostic factors in various malignancies (15)(16)(17)(18)(19)(20)(21). In previous reports on PD-L1 expression in thymic epithelial tumors, it was stated that high PD-L1 expression was associated with an advanced Masaoka-Koga stage and more aggressive histologies such as type B2/B3 thymoma or thymic carcinoma (22)(23)(24). In contrast, survival analyses based on PD-L1 expression were inconsistent, as one study determined a significant association between high PD-L1 expression and poor OS in an age-and sex-adjusted analysis, whereas the others did not find any prognostic impact.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic Value of Programmed Death Ligand 1 and Programmed Death 1 Expression in Thymic Carcinoma

Yokoyama

Miyoshi

Nakashima

et al. 2016

Clinical Cancer Research

115

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Purpose: The immune checkpoint of the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway is believed to play an important role in evasion of host antitumor immune surveillance in various malignancies; however, little is known about its role in thymic carcinoma. This study investigated PD-1/PD-L1 expression and its association with clinicopathologic features, the expression of immune-related proteins in tumor-infiltrating lymphocytes (TIL), and patient prognosis. Experimental Design: PD-L1 and PD-1 expression was evaluated by IHC in 25 thymic carcinoma tissue specimens. Copy number alterations of the PD-L1 gene in 11 cases were assessed in formalin-fixed, paraffin-embedded material using qRT-PCR. Results: Compared with normal subjects, 3 thymic carcinoma patients showed an increase in PD-L1 copy number, whereas 8 did not. PD-L1 was significantly overexpressed in cases with copy number gain as compared with normal cases. High PD-L1 expression was associated with higher disease-free and overall survival rates as compared to cases with low expression. Prognostic analysis revealed low PD-L1 expression and high number of PD-1+ TILs as significant predictors of poor survival, together with Masaoka–Koga stage IVa/IVb disease and incomplete resection. In the quantitative analysis of TILs, PD-L1 expression correlated proportionally with the number of infiltrating CTLs. Conclusions: Here, for the first time, we report that PD-L1 and PD-1 expression might be useful prognostic predictors in thymic carcinoma. Further studies are expected to substantiate the prognostic value of PD-L1 and PD-1 expression, and the potential efficacy of targeting the PD-1/PD-L1 pathway in thymic carcinoma via immunotherapy. Clin Cancer Res; 22(18); 4727–34. ©2016 AACR.

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“…Given the rarity of these tumors, such clinical trials might only be possible as multicenter regional or global endeavors to accrue a higher number of patients to provide sufficient power for a meaningful statistical analysis of outcome. Furthermore, although PD-L1 expression has been shown in at least a subset of thymoma and thymic carcinoma (12,17,18), randomized prospective clinical trials using anti-PD-1 or anti-PD-L1 antibodies have not been reported. National organizations such as ChART or the Japanese Association for Research of the Thymus (JART) and international associations such as the International Thymic Malignancy Interest Group (ITMIG) that are committed to research of TET would be ideal leaders for this effort.…”

mentioning

confidence: 99%

Non-surgical treatment of locally advanced thymic epithelial tumors—a need for multicenter trials

Roden

2016

J. Thorac. Dis.

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Immunohistochemical status of PD-L1 in thymoma and thymic carcinoma

Cited by 158 publications

References 36 publications

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

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

Prognostic Value of Programmed Death Ligand 1 and Programmed Death 1 Expression in Thymic Carcinoma

Non-surgical treatment of locally advanced thymic epithelial tumors—a need for multicenter trials

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