<i>In Situ</i> Tumor PD-L1 mRNA Expression Is Associated with Increased TILs and Better Outcome in Breast Carcinomas

Schalper, Kurt A.; Velcheti, Vamsidhar; Carvajal, Daniel; Wimberly, Hallie; Brown, Jennifer N.; Pusztai, Lajos; Rimm, David L.

doi:10.1158/1078-0432.ccr-13-2702

Cited by 448 publications

(430 citation statements)

References 41 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%

“…However, the prognostic effect of tumor PD-L1 expression varies across different cancer types and in different studies. [23][24][25] In addition, some studies have demonstrated the correlation of PD-L1 expression in TILs with clinical outcome. 26,27 Recently, a study with 37 penile cancer patients indicated that high level of PD-L1 expression in tumor cells is correlated with LN metastasis and poor CSS.…”

Section: Discussionmentioning

confidence: 99%

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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%

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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“…Many antibodies are available but lack specificity and reproducibility, 40,41 the optimal positivity cut-off is not defined, and staining interpretation suffers from subjectivity. These limitations led to the use of alternative methods, such as mRNA analysis based on in situ hybridization (ISH), 42 DNA microarrays, 43 or quantitative real-time polymerase chain reaction (qRT-PCR). 44 A positive relationship between protein and mRNA expression has been reported.…”

Section: Discussionmentioning

confidence: 99%

“…44 A positive relationship between protein and mRNA expression has been reported. 42 One limitation of DNA microarray-or qRT-PCR-based measurements is that they quantify expression level of both tumor and non-tumor cells present in the sample. This is particularly critical for carcinomas, although results are consistent with those reported using ISH.…”

Section: Discussionmentioning

confidence: 99%

PDL1 expression is an independent prognostic factor in localized GIST

et al. 2015

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Gastrointestinal stromal tumors (GIST) are the most frequently occurring digestive sarcomas. The prognosis of localized GIST is heterogeneous, notably for patients with an Armed Forces Institute of Pathology (AFIP) intermediate or high risk of relapse. Despite imatinib effectiveness, it is crucial to develop therapies able to overcome the resistance mechanisms. The immune system represents an attractive prognostic and therapeutic target. The Programmed cell Death 1 (PD1)/programmed cell death ligand 1 (PDL1) pathway is a key inhibitor of the immune response; recently, anti-PD1 and anti-PDL1 drugs showed very promising results in patients with solid tumors. However, PDL1 expression has never been studied in GIST. Our objective was to analyze PDL1 expression in a large series of clinical samples. We analyzed mRNA expression data of 139 operated imatinib-untreated localized GIST profiled using DNA microarrays and searched for correlations with histoclinical features including postoperative metastatic relapse. PDL1 expression was heterogeneous across tumors and was higher in AFIP low-risk than in high-risk samples, and in samples without than with metastatic relapse. PDL1 expression was associated with immunity-related parameters such as T-cell-specific and CD8C T-cell-specific gene expression signatures and probabilities of activation of interferon a (IFNa), IFNg, and tumor necrosis factor a (TNFa) pathways, suggesting positive correlation with a cytotoxic T-cell response. In multivariate analysis, the PDL1-low group was associated with a higher metastatic risk independently of the AFIP classification and the KIT mutational status. In conclusion, PDL1 expression refines the prediction of metastatic relapse in localized GIST and might improve our ability to better tailor adjuvant imatinib. In the metastatic setting, PDL1 expression might guide the use of PDL1 inhibitors, alone or associated with tyrosine kinase inhibitors.

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“…Therefore, PD-L1 is a valuable prognostic marker; the correlation between PD-L1 expression infiltration of tumor by lymphocytes (TILs) [16], high histological grade of tumor [17] and worse clinical outcome [18] is already determined. Nowadays research activities are focused on PD-1/ PD-L1 signaling through the application of humanized monoclonal antibodies (e.g., Nivolumab).…”

Section: Introductionmentioning

confidence: 99%