The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer

Mori, Hitomi; Kubo, Makoto; Yamaguchi, Rin; Nishimura, Reiki; Osako, Tomofumi; Arima, Nobuyuki; Okumura, Yasuhiro; Okido, Masayuki; Yamada, Mai; Kai, Masaya; Kishimoto, Junji; Oda, Yoshinao; Nakamura, Masafumi

doi:10.18632/oncotarget.14698

Cited by 109 publications

(87 citation statements)

References 37 publications

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“…PD‐L1 expression evaluated by IHC on untreated primary BC has been associated with both better and poorer clinical outcome. In particular, several authors reported poorer disease‐free survival (DFS)/recurrence‐free survival (RFS) and/or overall survival (OS) in cases of higher PD‐L1 expression on primary BC , especially in the TN subtype . These results seems to be consistent with the previously mentioned correlation between PD‐L1 expression and unfavorable clinicopathological BC features, thus possibly indicating that PD‐L1 expression may be part of the immune evasion process taking place in the context of tumor microenvironment .…”

Section: Methodssupporting

confidence: 77%

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

2019

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In the light of recent advances in the immunotherapy field for breast cancer (BC) treatment, especially in the triple‐negative subtype, the identification of reliable biomarkers capable of improving patient selection is paramount, because only a portion of patients seem to derive benefit from this appealing treatment strategy. In this context, the role of programmed cell death ligand 1 (PD‐L1) as a potential prognostic and/or predictive biomarker has been intensively explored, with controversial results. The aim of the present review is to collect available evidence on the biological relevance and clinical utility of PD‐L1 expression in BC, with particular emphasis on technical aspects, prognostic implications, and predictive value of this promising biomarker. Implications for Practice In the light of the promising results coming from trials of immune checkpoint inhibitors for breast cancer treatment, the potential predictive and/or prognostic role of programmed cell death ligand 1 (PD‐L1) in breast cancer has gained increasing interest. This review provides clinicians with an overview of the available clinical evidence regarding PD‐L1 as a biomarker in breast cancer, focusing on both data with a possible direct impact on clinic and methodological pitfalls that need to be addressed in order to optimize PD‐L1 implementation as a clinically useful tool for breast cancer management.

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Section: Methodssupporting

confidence: 77%

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

2019

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“…There have been conflicting results in the literature as to whether PD‐L1 expression is a favorable or adverse prognostic factor for breast cancer patients managed with standard therapy. Most of the published studies have dealt with patients with diverse subtypes of breast cancer, with the exception of several studies which focused on TNBC exclusively . The discordance of reported results may relate to differences in methods of assessment, numeric thresholds, antibody clones or composition of cohorts.…”

Section: Discussionsupporting

confidence: 50%

“…Recently, the combination of PD‐L1 and tumor‐infiltrating lymphocytes (TILs) has been investigated in TNBC, and the reported findings confirm the importance of examining both PD‐L1 and TILs for clinical outcome prediction . In the current study, we evaluated PD‐L1 and a set of other relevant immune markers in relation to their association with clinical outcome in a series of HER2‐positive cases.…”

Section: Introductionmentioning

confidence: 99%

PD-L1 expression and CD8-positive T cells are associated with favorable survival in HER2-positive invasive breast cancer

et al. 2018

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Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key physiologic suppressors of the cytotoxic immune reaction. However, to date, the combination of PD1/PD-L1 expression and tumor-infiltrating lymphocytes (TILs) and antigen-presenting cells has been only minimally reported in breast carcinoma, in particular in relation to HER2-positive cases. The goal of this study was to evaluate both cellular tumoral immune reaction and PD-L1/PD1 distribution in HER2-positive cases, as well as any associations with clinical outcome using conventional chemotherapy combined with HER2 blocking. Multicolor immunohistochemical multiplex assays simultaneously demonstrating PD1, PD-L1, and CD8 or PD-L1, CD3, and CD163 were performed on tissue microarrays (TMA) representing 216 pretreatment cases of HER2-positive invasive breast carcinoma. PD-L1 expression was identified in 38 cases (18%), including 12 cases (6%) with PD-L1 labeling of tumor cells and 26 cases (12%) with PD-L1 labeling of immune cells only. Ten of 12 cases with PD-L1 staining of tumor cells showed staining of associated immune cells as well. With this assay method, PD1 was detectable in many fewer cases (6 cases or 3%). PD-L1 expression was positively associated with high Nottingham grade, negative ER and PR, the absence of lymph node metastasis, and high levels of CD8 cells. The overall survival by univariate analysis was positively associated with lower tumor stage, the absence of lymph node metastasis, PD-L1 expression, and high levels of CD8 cells. Therefore, our data suggest cytotoxic immune reaction mediated by CD8-positive T cells and PD-L1 expression may predict a better outcome in patients with HER2-positive breast carcinoma managed with conventional chemotherapy and HER2-blocking therapy. These findings recommend clinical trials utilizing checkpoint blocking immunotherapy in some form for HER2-positive breast cancer.

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“…Anti-PD-L1 rabbit monoclonal antibody from Cell Signaling (clone E1L3N, #13684)(14–16) was titered on PD-L1 negative (Colo205, H23), low (SU-DHL1), medium (H441) and high (H820) expressing cell line cells that had been spiked into healthy donor blood and run on the automated digital microscopy platform to evaluate the analytical performance of the antibody. PD-L1 expression levels demonstrated excellent antibody sensitivity and specificity for PD-L1 protein.…”

Section: Methodsmentioning

confidence: 99%

Cellular Expression of PD-L1 in the Peripheral Blood of Lung Cancer Patients is Associated with Worse Survival

Boffa

Graf

Hoag³

et al. 2017

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background Lung cancer treatment has become increasingly dependent upon invasive biopsies to profile tumors for personalized therapy. Recently, tumor expression of PD-L1 has gained interest as a potential predictor of response to immunotherapy. Circulating biomarkers present an opportunity for tumor profiling without the risks of invasive procedures. We characterized PD-L1 expression within populations of nucleated cells in the peripheral blood of lung cancer patients in hopes of expanding the role of liquid biopsy in this setting. Methods Peripheral blood samples from a multi-institutional prospective study of patients with clinical diagnosis of lung cancer were subjected to cytomorphometric and immunohistochemical evaluation using single-cell, automated slide-based, digital pathology. PD-L1 expression was determined by immunofluorescence. Results PD-L1 expression was detected within peripheral circulating cells associated with malignancy (CCAM) in 26/112(23%) non-small cell lung cancer patients. Two distinct populations of nucleated, non-hematolymphoid, PD-L1 expressing cells were identified; cytokeratin positive (CK+, PD-L1+, CD45−) and cytokeratin negative (CK−, PD-L1+, CD45−) cells, both with cytomorphometric features (size, nuclear to cytoplasm ratio) consistent with tumor cells. Patients with >1.1 PD-L1(+) cell/mL (n=14/112) experienced worse overall survival than patients with ≤1.1 PD-L1(+) cell/ml (2-yearOS:31.2% vs 78.8%, p=0.00159). In a Cox model adjusting for stage, high PD-L1(+) cell burden remained a significant predictor of mortality (HR=3.85, 95%CI:1.64–9.09, p=0.002). Conclusions PD-L1 expression is detectable in two distinct cell populations in the peripheral blood of lung cancer patients and is associated with worse survival.

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The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer

Cited by 109 publications

References 37 publications

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

Programmed Cell Death Ligand 1 in Breast Cancer: Technical Aspects, Prognostic Implications, and Predictive Value

PD-L1 expression and CD8-positive T cells are associated with favorable survival in HER2-positive invasive breast cancer

Cellular Expression of PD-L1 in the Peripheral Blood of Lung Cancer Patients is Associated with Worse Survival

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