Programmed death ligand 1 expression in triple‐negative breast cancer is associated with tumour‐infiltrating lymphocytes and improved outcome

Beckers, Rhiannon; Selinger, Christina; Vilain, Ricardo E.; Madore, Jason; Wilmott, James S.; Harvey, Kate; Holliday, Anne; Cooper, Caroline; Robbins, Elizabeth; Gillett, David J.; Kennedy, Catherine; Gluch, Laurence; Carmalt, Hugh; Mak, Cindy; Warrier, Sanjay; Gee, Harriet E.; Chan, Charles; McLean, Anna; Walker, Emily; McNeil, Catriona M.; Beith, Jane; Swarbrick, Alexander; Scolyer, Richard A.; O’Toole, Sandra A.

doi:10.1111/his.12904

Cited by 199 publications

(204 citation statements)

References 33 publications

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“…These studies are difficult to compare due to different cut-offs used for PD-L1 positivity (e.g., cut-off at 1 or 5%), staining evaluated on cancer cells or immune infiltrates, the kind of antibodies employed, as well as the use of different assays (IHC, gene expression profiling, or in situ RNA hybridization); however, some common findings have emerged from these reports. First, PD-L1 expression positively associates with the presence of immune-infiltrates [39,40,43,48,49,50,51,52,53,54]. Second, TNBC (or basal-like) tumors express PD-L1 more frequently than other subtypes [39,40,51,55].…”

Section: Pd-l1 Expression In Breast Cancermentioning

confidence: 99%

“…Second, TNBC (or basal-like) tumors express PD-L1 more frequently than other subtypes [39,40,51,55]. The main finding of studies that assessed PD-L1 expression in breast cancer are summarized in supplemental table 2 (www.karger.com/?DOI=445335) [39,40,43,48,49,50,51,52,53,54,55,56,57]. …”

Section: Pd-l1 Expression In Breast Cancermentioning

confidence: 99%

“…In another study with 161 TNBCs, PD-L1 positivity using a 1% cut-off was even higher: 64% for tumor cell membranous staining, 80% for cytoplasmic staining, and 93% for stromal staining [52]. Even with a 5% cut-off, the proportion of PD-L1-positive tumors remains high: 60, 77, and 93%, for tumor cell membranous, cytoplasmic, and stromal staining, respectively [52].…”

Section: Pd-l1 Expression In Breast Cancermentioning

confidence: 99%

“…Even with a 5% cut-off, the proportion of PD-L1-positive tumors remains high: 60, 77, and 93%, for tumor cell membranous, cytoplasmic, and stromal staining, respectively [52]. It is possible that these discrepancies are at least in part influenced by the kind of antibody used, therefore highlighting the urgent need for harmonization procedures [58,59].…”

Section: Pd-l1 Expression In Breast Cancermentioning

confidence: 99%

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Checkpoint Inhibitors and Their Application in Breast Cancer

et al. 2016

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Immune checkpoints are crucial for the maintenance of self-tolerance and for the modulation of immune responses in order to minimize tissue damage. Tumor cells take advantage of these mechanisms to evade immune recognition. A significant proportion of tumors, including breast cancers, can express co-inhibitory molecules that are important formediating the escape from T cell-mediated immune surveillance. The interaction of inhibitory receptors with their ligands can be blocked by specific molecules. Monoclonal antibodies (mAbs) directed against the cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and, more recently, against the programmed cell death protein 1 (PD1), have been approved for the therapy of melanoma (anti-CTLA4 and anti-PD1 mAbs) and non-small cell lung cancer (anti-PD1 mAbs). Moreover, inhibition of PD1 signaling has shown extremely promising signs of activity in breast cancer. An increasing number of molecules directed against other immune checkpoints are currently under clinical development. In this review, we summarize the evidence supporting the implementation of checkpoint inhibition in breast cancer by reviewing in detail data on PD-L1 expression and its regulation. In addition, opportunities to boost anti-tumor immunity in breast cancer with checkpoint inhibitor-based immunotherapies alone and in combination with other treatment options will be discussed.

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Section: Pd-l1 Expression In Breast Cancermentioning

confidence: 99%

Section: Pd-l1 Expression In Breast Cancermentioning

confidence: 99%

Section: Pd-l1 Expression In Breast Cancermentioning

confidence: 99%

Section: Pd-l1 Expression In Breast Cancermentioning

confidence: 99%

See 2 more Smart Citations

Checkpoint Inhibitors and Their Application in Breast Cancer

et al. 2016

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“…PD-L1 can be expressed both on tumor cells and infiltrating immune cells and may correlate with favorable prognosis and response to immune checkpoint inhibitor therapy in diverse tumor types including non-small cell lung carcinoma, melanoma, and urothelial carcinoma (10)(11)(12)(13)(14). PD-L1 expression in invasive breast carcinomas is most common in tumor cells in triple-negative cancers and correlates closely with the extent of the immune infiltrate (15,16).…”

Section: Introductionmentioning

confidence: 99%

Relationship of the Breast Ductal Carcinoma In Situ Immune Microenvironment with Clinicopathological and Genetic Features

Hendry

Pang

Byrne

et al. 2017

Clinical Cancer Research

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Purpose: The immune microenvironment of breast ductal carcinoma in situ (DCIS) has yet to be fully explored, and the relationship of immune cells to genetic features of DCIS is unknown.Experimental Design: We quantified tumor associated lymphocytes (TIL) and evaluated PD-L1 protein levels by immunohistochemistry in a cohort of pure DCIS (138 and 79 cases, respectively), some of which had copy number (n ¼ 55) and mutation data (n ¼ 20).Results: TILs were identified in the stroma surrounding DCIS (119/138, 86%) and present at a median TIL score of 5% (range, 0%-90%). Most DCIS were negative for tumor cell PD-L1 staining (89%), but 25% of cases were positive for immune cell staining. We observed that, as in invasive breast cancer, TILs and PD-L1 positivity were significantly greater in high-grade (P ¼ 0.002/0.035), ER-negative (P ¼ 0.02/0.02), and ERBB2-amplified tumors (P < 0.001/0.048). Comedo necrosis was significantly positively associated with TILs (P < 0.0001) but not with PD-L1. The TILs score was significantly higher in cases with TP53 mutation (P ¼ 0.03) but not with PIK3CA or GATA3 mutation. In the cases with copy number data, both the fraction of the genome altered and the number of telomeric imbalances were significantly positively correlated with TILs (both P < 0.001). This result strongly contrasted with invasive breast cancer data, where aneuploidy was not correlated to TIL levels.Conclusions: Although a small cohort, our data suggest a preliminary model by which the progression of DCIS to invasive carcinoma may involve an altered relationship of tumor copy number with the immune microenvironment, possibly by the immunoediting of the tumor. Clin Cancer Res; 23(17); 5210-7.Ó2017 AACR.

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Nuclear Aurora kinase A triggers programmed death‐ligand 1‐mediated immune suppression by activating MYC transcription in triple‐negative breast cancer

Sun

Zhou

et al. 2021

Cancer Communications

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Background: Increasing studies have reported that oncogenes regulate components of the immune system, suggesting that this is a mechanism for tumorigenesis. Aurora kinase A (AURKA), a serine/threonine kinase, is involved in cell mitosis and is essential for tumor cell proliferation, metastasis, and drug resistance. However, the mechanism by which AURKA is involved in immune response regulation is unclear. Therefore, this study aimed to investigate the role of AURKA in immune regulation in triple-negative breast cancer (TNBC). Methods: Peripheral blood mononuclear cells (PBMCs) were co-cultured with TNBC cells. The xCELLigence Real-Time Cell Analyzer-MP system was used to detect the killing efficiency of immune cells on TNBC cells. The expression of immune effector molecules was tested by quantitative real-time polymerase chain reaction (qRT-PCR) to evaluate immune function. Furthermore, to validate AURKA-regulated immune response in vivo, 4T1 murine breast cancer cell line with AURKA overexpression or downregulation was engrafted into BALB/c mice. The distribution and proportion of immune cells in tumors were further evaluated by immunohistochemistry and flow cytometry.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Programmed death ligand 1 expression in triple‐negative breast cancer is associated with tumour‐infiltrating lymphocytes and improved outcome

Cited by 199 publications

References 33 publications

Checkpoint Inhibitors and Their Application in Breast Cancer

Checkpoint Inhibitors and Their Application in Breast Cancer

Relationship of the Breast Ductal Carcinoma In Situ Immune Microenvironment with Clinicopathological and Genetic Features

Nuclear Aurora kinase A triggers programmed death‐ligand 1‐mediated immune suppression by activating MYC transcription in triple‐negative breast cancer

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