PD-L1 expression is associated with tumor-infiltrating T cells and favorable prognosis in high-grade serous ovarian cancer

Webb, John R.; Milne, Katy; Kroeger, David R.; Nelson, Brad H.

doi:10.1016/j.ygyno.2016.03.008

Cited by 280 publications

(296 citation statements)

References 40 publications

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“…Several researches also described similar association. 23,31,32 This correlation was in accordance with the previous finding that IFNg, expressed by activated CD8 C T cells, can induce PD-L1 expression in the surrounding tumor cells. 33 Moreover, seven patients (Table 2) with absent or focal TILs still presented PD-L1 positivity.…”

Section: Discussionsupporting

confidence: 92%

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: 92%

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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“…PD-1/PD-L1 blockade caused tumor regression in a syngeneic EOC mouse model, thus supporting the relevance of this regulatory pathway in ovarian carcinogenesis (38).…”

Section: Epithelial Ovarian Cancersupporting

confidence: 52%

“…Conflicting data emerge from the literature about the prognostic relevance of PD-1 and PD-L1 expression in EOC and these discordant results may reflect different techniques for PD-1 and PD-L1 assessment, different cut-off values for tumor cell staining, as well aspatients' heterogeneity (34)(35)(36)(37)(38).…”

Section: Epithelial Ovarian Cancermentioning

confidence: 99%

Immune Checkpoint Inhibitors in Gynecological Cancers: Update of Literature and Perspectives of Clinical Research

2017

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“…For example, in ovarian cancer, the differential expression of immunological markers related to the PD-1/PD-L1 pathway in blood can be used as potential diagnostic and prognostic markers [13]. PD-L1 is also expressed by macrophages in ovarian cancer and is strongly associated with both effector and regulatory tumour infiltrating lymphocyte (TIL) subsets [14]. Interestingly, Yang et al revealed a previously unrecognized mechanism through which chemotherapy induces tumour immune evasion via the up-regulation of PD-L1 in bone marrow stromal cells, providing new evidence for the combination of chemotherapy and anti-PD-L1/PD-1 as an effective strategy for the treatment of lymphoma and other cancers [15].…”

Section: Introductionmentioning

confidence: 99%

Membranous and Cytoplasmic Expression of PD-L1 in Ovarian Cancer Cells

Xie

Huang

et al. 2017

Cell Physiol Biochem

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Background: Expression of programmed death-ligand 1 (PD-L1) on tumor cells represents a powerful immune evasion pathway, but the role of intracellular or cytoplasmic PD-L1 has not been investigated in ovarian cancer cells. Methods: Flow cytometry (FCM), Real-time PCR (qPCR), immunohistochemistry (IHC) and western blot were used to determine the expression of PD-L1 in ovarian cancer cells. The cytokines detected in the tumor or tumor associated macrophage (TAM) were used to treat cancer cells. PD-L1 blockade and silencing were used to elucidate the functional significance of cancer-related PD-L1 expression. Results: Based on the results presented, PD-L1 was found variably expressed in the cytoplasm and the cell surface of both HO8910 and SKOV3 cells. TAM or IFN-γ, TNF-α, IL-10 and IL-6 released from TAM stimulated the expression of PD-L1 at the surface of the cancer cells. The IHC results were consistent with the data in vitro showing infiltration of TAM correlated with membranous PD-L1. The increases of PD-L1 at the surface were not due to a shift in the proportion of surface versus intracellular protein, but the contribution of extracellular signal-regulated kinase (ERK)1/2 and phosphoinositide 3-kinase (PI3K) pathway activation. As a consequence, inducible membranous PD-L1 expression on SKOV3 inhibited CD8⁺ T cell function, and cytoplasmic PD-L1 promoted cancer cell growth. Additionally, in mouse models, both PD-L1 and PD-1 mAb resulted in tumor growth inhibition and demonstrated a potential to decrease the number of PD-1⁺CD8⁺T cells. Conclusion: We conclude that TAM induced PD-L1 on the cancer cells represents an immune evasion mechanism. The observations confirm the therapeutic potential of PD-L1/PD-1 mAb to reactivate anti-tumor immunity in ovarian cancer.

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PD-L1 expression is associated with tumor-infiltrating T cells and favorable prognosis in high-grade serous ovarian cancer

Cited by 280 publications

References 40 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

Immune Checkpoint Inhibitors in Gynecological Cancers: Update of Literature and Perspectives of Clinical Research

Membranous and Cytoplasmic Expression of PD-L1 in Ovarian Cancer Cells

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