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Pd-l1 breast cancer

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https://www.readbyqxmd.com/read/28537889/immune-signature-of-metastatic-breast-cancer-identifying-predictive-markers-of-immunotherapy-response
#1
Ji-Yeon Kim, Eunjin Lee, Kyunghee Park, Woong-Yang Park, Hae Hyun Jung, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
In breast cancer (BC), up to 10-20% patients were known to have clinical benefit with immune checkpoint inhibitors, and biomarkers are needed for optimal use of this multi-potential therapeutic strategy. Accordingly, we conducted an experiment to identify expression of genes associated with immune checkpoints that represent potential targets of cancer immunotherapy. We performed whole-transcriptome sequencing and whole-exome sequencing using 37 refractory BC specimens. In the immune pathway gene set expression analysis, we found that HER2 expression and previous taxane treatment were positively correlated with high expression of immune gene set expression (p = 0...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28488168/the-therapeutic-candidate-for-immune-checkpoint-inhibitors-elucidated-by-the-status-of-tumor-infiltrating-lymphocytes-tils-and-programmed-death-ligand-1-pd-l1-expression-in-triple-negative-breast-cancer-tnbc
#2
Nobumoto Tomioka, Manabu Azuma, Mayuko Ikarashi, Mitsugu Yamamoto, Masako Sato, Ken-Ichi Watanabe, Katsushige Yamashiro, Masato Takahashi
BACKGROUND: The status of tumor-infiltrating lymphocytes (TILs) is a prognostic factor for triple negative breast cancer (TNBC). Recent studies have shown that programmed cell death 1 (PD-1) or programmed death ligand 1 (PD-L1) is expressed on T lymphocytes or tumor cells modulating antitumor immunity. The regulation of immune checkpoints between tumor cells and T lymphocytes may serve as a target for improvement of TNBC prognosis. We investigated TILs and PD-L1 status in TNBCs before or after preoperative systemic therapy (PST) to elucidate the clinical significance of PD-L1 expression...
May 9, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28471952/prognostic-significance-of-pd-l1-in-solid-tumor-an-updated-meta-analysis
#3
Qianqian Wang, Fang Liu, Lei Liu
BACKGROUND: An increasing number of studies have examined the ability of programmed death-ligand 1 (PD-L1) to function as a marker for tumor prognosis. However, whether PD-L1 expression is a prognostic factor for the poor outcomes in many human cancers remains controversial. This study aims to investigate the prognostic role of PD-L1 expression through a meta-analysis update of 60 studies. METHODS: The studies were identified by searching PubMed, Embase, Google Scholar, and Cochrane Library, and were assessed by further quality evaluation...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28465490/type-i%C3%AE-phosphatidylinositol-phosphate-kinase-regulates-pd-l1-expression-by-activating-nf-%C3%AE%C2%BAb
#4
Junli Xue, Chunhua Chen, Manlong Qi, Yan Huang, Lin Wang, Yong Gao, Haidong Dong, Kun Ling
The programmed death-ligand 1 (PD-L1), by binding to PD-1 on the surface of immune cells, activates a major immune checkpoint pathway. Elevated expression of PD-L1 in tumor cells mediates tumor-induced T-cell exhaustion and immune suppression; therefore protect the survival of tumor cells. Although blockade of the PD-1/PD-L1 axis exhibits great potential in cancer treatment, mechanisms driving the up-regulation of PD-L1 in tumor cells remain not fully understood. Here we found that type Iγ phosphatidylinositol 4-phosphate (PtdIns(4)P) 5-kinase (PIPKIγ) is required for PD-L1 expression in triple negative breast cancer cells...
April 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28453554/prognostic-value-of-pd-l1-expression-in-tumor-infiltrating-immune-cells-in-cancers-a-meta-analysis
#5
Tiancheng Zhao, Changfeng Li, Yanhua Wu, Bingjin Li, Bin Zhang
Programmed death-ligand 1 (PD-L1) is a promising target of cancer immune therapy. It not only expressed in tumor cells (TCs) but also up regulated in tumor infiltrating immune cells (TIICs). Although the previous meta-analysis have shown that PD-L1 expression in TCs was a valuable biomarker in predicting cancer prognosis, but few researches systematic evaluated the association between its expression in TIICs and survival of cancer patients. Thus, we performed this meta-analysis to evaluate the prognostic value of PD-L1 expression in TIICs in different types of cancers...
2017: PloS One
https://www.readbyqxmd.com/read/28430626/expression-of-pd-l1-and-prognosis-in-breast-cancer-a-meta-analysis
#6
Minghui Zhang, Houbin Sun, Shu Zhao, Yan Wang, Haihong Pu, Yan Wang, Qingyuan Zhang
The associations between programmed cell death ligand 1 (PD-L1) and the prognosis of various cancers have always been a research topic of considerable interest. However, the prognostic value of PD-L1 in breast cancer patients remains a controversial subject. We aimed to assess the association between PD-L1 protein expression and clinicopathological features and the impact of this relationship on breast cancer survival. We performed a systematic search of the PubMed, EMBASE, and Cochrane Library databases to determine the correlations among PD-L1 expression, clinicopathological features and overall survival (OS)...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422766/an-immunoscore-using-pd-l1-cd68-and-tumor-infiltrating-lymphocytes-tils-to-predict-response-to-neoadjuvant-chemotherapy-in-invasive-breast-cancer
#7
Lauren E McLemore, Murali Janakiram, Joseph Albanese, Nella Shapiro, Yungtai Lo, Xingxing Zang, Susan Fineberg
Response to neoadjuvant chemotherapy (NAC) in invasive breast cancer (IBC) is partly regulated by the immune microenvironment. We evaluated immune checkpoint PD-L1 expression, presence of CD68+ cells of macrophage/monocytic lineage and stromal tumor-infiltrating lymphocytes (TILs) in prechemotherapy biopsies and correlated with NAC response. We studied 76 cases of IBC. Prechemotherapy biopsies with >30% TILs were considered lymphocyte-rich IBC. We performed immunohistochemistry for PD-L1 and CD68. Prechemotherapy cores showing >1% PD-L1+ immune or tumor cells were considered positive...
April 18, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28415798/tumor-derived-il-18-induces-pd-1-expression-on-immunosuppressive-nk-cells-in-triple-negative-breast-cancer
#8
In Hae Park, Han Na Yang, Kyoung Joo Lee, Tae-Sik Kim, Eun Sook Lee, So-Youn Jung, Youngmee Kwon, Sun-Young Kong
PURPOSE: While the inflammatory cytokine interleukin-18 (IL-18) is known to activate natural killer (NK) cells, its precise role in cancer is controversial. In this study, we investigated the role of tumor-derived IL-18 on peripheral blood NK cells in breast cancer patients. RESULTS: In breast cancer cell lines, IL-18 was expressed and secreted in the triple-negative breast cancer (TNBC) cell lines MDA-MB-231 and HCC-70 but not in MCF-7 cells. The immature and non-cytotoxic CD56dimCD16dim/- NK cell fraction was increased following co-culture with MDA-MB-231 cells, and this increase was not observed with tumor cells transfected with siRNA for IL-18 or in MCF-7 cells...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28405494/overcoming-resistance-to-her2-targeted-therapy-with-a-novel-her2-cd3-bispecific-antibody
#9
Andres Lopez-Albaitero, Hong Xu, Hongfen Guo, Linlin Wang, Zhihao Wu, Hoa Tran, Sarat Chandarlapaty, Maurizio Scaltriti, Yelena Janjigian, Elisa de Stanchina, Nai-Kong V Cheung
T-cell-based therapies have emerged as one of the most clinically effective ways to target solid and non-solid tumors. HER2 is responsible for the oncogenesis and treatment resistance of several human solid tumors. As a member of the HER family of tyrosine kinase receptors, its over-activity confers unfavorable clinical outcome. Targeted therapies directed at this receptor have achieved responses, although development of resistance is common. We explored a novel HER2/CD3 bispecific antibody (HER2-BsAb) platform that while preserving the anti-proliferative effects of trastuzumab, it recruits and activates non-specific circulating T-cells, promoting T cell tumor infiltration and ablating HER2(+) tumors, even when these are resistant to standard HER2-targeted therapies...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28404866/combined-antiangiogenic-and-anti-pd-l1-therapy-stimulates-tumor-immunity-through-hev-formation
#10
Elizabeth Allen, Arnaud Jabouille, Lee B Rivera, Inge Lodewijckx, Rindert Missiaen, Veronica Steri, Kevin Feyen, Jaime Tawney, Douglas Hanahan, Iacovos P Michael, Gabriele Bergers
Inhibitors of VEGF (vascular endothelial growth factor)/VEGFR2 (vascular endothelial growth factor receptor 2) are commonly used in the clinic, but their beneficial effects are only observed in a subset of patients and limited by induction of diverse relapse mechanisms. We describe the up-regulation of an adaptive immunosuppressive pathway during antiangiogenic therapy, by which PD-L1 (programmed cell death ligand 1), the ligand of the negative immune checkpoint regulator PD-1 (programmed cell death protein 1), is enhanced by interferon-γ-expressing T cells in distinct intratumoral cell types in refractory pancreatic, breast, and brain tumor mouse models...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28404865/dual-angiopoietin-2-and-vegfa-inhibition-elicits-antitumor-immunity-that-is-enhanced-by-pd-1-checkpoint-blockade
#11
Martina Schmittnaegel, Nicolò Rigamonti, Ece Kadioglu, Antonino Cassará, Céline Wyser Rmili, Anna Kiialainen, Yvonne Kienast, Hans-Joachim Mueller, Chia-Huey Ooi, Damya Laoui, Michele De Palma
Pathological angiogenesis is a hallmark of cancer and a therapeutic target. Vascular endothelial growth factor A (VEGFA) and angiopoietin-2 (ANGPT2; also known as ANG2) are proangiogenic cytokines that sustain tumor angiogenesis and limit antitumor immunity. We show that combined ANGPT2 and VEGFA blockade by a bispecific antibody (A2V) provided superior therapeutic benefits, as compared to the single agents, in both genetically engineered and transplant tumor models, including metastatic breast cancer (MMTV-PyMT), pancreatic neuroendocrine tumor (RIP1-Tag2), and melanoma...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28377497/atezolizumab-extends-survival-for-breast-cancer
#12
(no author information available yet)
The anti-PD-L1 drug atezolizumab produced durable responses among 10% of patients with triple-negative breast cancer in a large phase I trial presented at the American Association for Cancer Research Annual Meeting 2017. The therapy proved safe, with the highest response rates seen in women who received the drug as a first-line therapy and in those with elevated PD-L1 levels and other tumor biomarkers.
April 4, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28346916/pd-1-pd-l1-pathway-in-breast-cancer
#13
Florian Schütz, Stefan Stefanovic, Luisa Mayer, Alexandra von Au, Christoph Domschke, Christof Sohn
The programmed cell death-1 receptor (PD-1) is an immune checkpoint inhibitor which is expressed on the surface of immune effector cells. It is activated mainly by PD-L1 which can be expressed by all human cells. The PD-1/PD-L1 pathway plays a subtle role in maintaining peripheral T-lymphocyte tolerance and regulating inflammation. In cancer, the expression of PD-L1 seems to be one of the major immune escape mechanisms. Many studies have shown efficacy of blocking PD-1 or PD-L1 with specific antibodies like pembrolizumab or atezulizumab...
2017: Oncology Research and Treatment
https://www.readbyqxmd.com/read/28255028/gene-signature-driving-invasive-mucinous-adenocarcinoma-of-the-lung
#14
Minzhe Guo, Koichi Tomoshige, Michael Meister, Thomas Muley, Takuya Fukazawa, Tomoshi Tsuchiya, Rebekah Karns, Arne Warth, Iris M Fink-Baldauf, Takeshi Nagayasu, Yoshio Naomoto, Yan Xu, Marcus A Mall, Yutaka Maeda
Though invasive mucinous adenocarcinoma of the lung (IMA) is pathologically distinctive, the molecular mechanism driving IMA is not well understood, which hampers efforts to identify therapeutic targets. Here, by analyzing gene expression profiles of human and mouse IMA, we identified a Mucinous Lung Tumor Signature of 143 genes, which was unexpectedly enriched in mucin-producing gastrointestinal, pancreatic, and breast cancers. The signature genes included transcription factors FOXA3, SPDEF, HNF4A, mucins MUC5AC, MUC5B, MUC3, and an inhibitory immune checkpoint VTCN1/B7-H4 (but not PD-L1/B7-H1)...
April 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28254786/clinical-impact-of-tumor-dna-repair-expression-and-t-cell-infiltration-in-breast-cancers
#15
Andrew R Green, Mohammed A Aleskandarany, Reem Ali, Eleanor Grace Hodgson, Suha Atabani, Karen De Souza, Emad Rakha, Ian O Ellis, Srinivasan Madhusudan
Impaired DNA repair drives mutagenicity, which increases neoantigen load and immunogenicity. We investigated the expression of proteins involved in the DNA damage response (ATM, Chk2), double-strand break repair (BRCA1, BLM, WRN, RECQL4, RECQL5, TOPO2A, DNA-PKcs, Ku70/Ku80), nucleotide excision repair (ERCC1), base excision repair (XRCC1, pol β, FEN1, PARP1), and immune responses (CD8, PD-1, PD-L1, FOXP3) in 1269 breast cancers and validated our findings in an independent estrogen receptor (ER)- cohort (n = 279)...
March 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28230773/programmed-death-ligand-1-pd-l1-tumor-expression-is-associated-with-a-better-prognosis-and-diabetic-disease-in-triple-negative-breast-cancer-patients
#16
Gerardo Botti, Francesca Collina, Giosuè Scognamiglio, Federica Rao, Valentina Peluso, Rossella De Cecio, Michela Piezzo, Gabriella Landi, Michelino De Laurentiis, Monica Cantile, Maurizio Di Bonito
Triple Negative Breast Cancers (TNBC) subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1) is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28228704/pd-1-and-pd-l1-immune-checkpoint-blockade-to-treat-breast-cancer
#17
REVIEW
Andreas D Hartkopf, Florin-Andrei Taran, Markus Wallwiener, Christina B Walter, Bernhard Krämer, Eva-Maria Grischke, Sara Y Brucker
Immune checkpoint inhibition represents a major recent breakthrough in the treatment of malignant diseases including breast cancer. Blocking the programmed death receptor-1 (PD-1) and its ligand, PD-L1, has shown impressive antitumor activity and may lead to durable long-term disease control, especially in the triple-negative subtypes of breast cancer (TNBC). Although immune checkpoint blockade is generally well tolerated, specific immune-related adverse events (irAEs) may occur. This review summarizes the clinical efficacy, perspectives, and future challenges of using PD-1/PD-L1-directed antibodies in the treatment of breast cancer...
December 2016: Breast Care
https://www.readbyqxmd.com/read/28197390/the-immune-checkpoint-ligand-pd-l1-is-upregulated-in-emt-activated-human-breast-cancer-cells-by-a-mechanism-involving-zeb-1-and-mir-200
#18
Muhammad Zaeem Noman, Bassam Janji, Abderemane Abdou, Meriem Hasmim, Stéphane Terry, Tuan Zea Tan, Fathia Mami-Chouaib, Jean Paul Thiery, Salem Chouaib
PD-L1 expression and regulation by mesenchymal tumor cells remain largely undefined. Here, we report that among different EMT-activated MCF7 human breast cancer cell clones, PD-L1 was differentially upregulated in MCF7 sh-WISP2, MCF7-1001/2101, and MDA-MB-231 cells but not in MCF7 SNAI1 and MCF7 SNAI1-6SA cells. Mechanistic investigations revealed that siRNA silencing of ZEB-1, but not SNAI1, TWIST, or SLUG and overexpression of miR200 family members in MCF7 sh-WISP2 cells strongly decreased PD-L1 expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197375/tumor-infiltrating-lymphocyte-composition-organization-and-pd-1-pd-l1-expression-are-linked-in-breast-cancer
#19
Laurence Buisseret, Soizic Garaud, Alexandre de Wind, Gert Van den Eynden, Anais Boisson, Cinzia Solinas, Chunyan Gu-Trantien, Céline Naveaux, Jean-Nicolas Lodewyckx, Hugues Duvillier, Ligia Craciun, Isabelle Veys, Denis Larsimont, Martine Piccart-Gebhart, John Stagg, Christos Sotiriou, Karen Willard-Gallo
The clinical relevance of tumor-infiltrating lymphocytes (TIL) in breast cancer (BC) has been clearly established by their demonstrated correlation with long-term positive outcomes. Nevertheless, the relationship between protective immunity, observed in some patients, and critical features of the infiltrate remains unresolved. This study examined TIL density, composition and organization together with PD-1 and PD-L1 expression in freshly collected and paraffin-embedded tissues from 125 patients with invasive primary BC...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28195880/pd-l1-expression-and-intratumoral-heterogeneity-across-breast-cancer-subtypes-and-stages-an-assessment-of-245-primary-and-40-metastatic-tumors
#20
Erik A Dill, Alejandro A Gru, Kristen A Atkins, Lisa A Friedman, Margaret E Moore, Timothy N Bullock, Janet V Cross, Patrick M Dillon, Anne M Mills
Tumor expression of programmed cell death ligand 1 (PD-L1) is associated with immune evasion in a variety of malignancies, including a subset of triple-negative breast carcinomas, and may mark cancers as susceptible to PD-1/PD-L1 inhibitor therapies. We herein characterize PD-L1 expression in breast cancers across the full range of histomorphologies and investigate its intratumoral heterogeneity and fidelity across primaries and metastases. A total of 245 primary and 40 metastatic (20 nodal, 20 distant) breast carcinomas were evaluated with PD-L1 immunohistochemistry on tissue microarray...
March 2017: American Journal of Surgical Pathology
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