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Pd-l1 breast cancer

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https://www.readbyqxmd.com/read/28721684/pharmacokinetics-microscale-distribution-and-dosimetry-of-alpha-emitter-labeled-anti-pd-l1-antibodies-in-an-immune-competent-transgenic-breast-cancer-model
#1
Jessie R Nedrow, Anders Josefsson, Sunju Park, Tom Bäck, Robert F Hobbs, Cory Brayton, Frank Bruchertseifer, Alfred Morgenstern, George Sgouros
BACKGROUND: Studies combining immune checkpoint inhibitors with external beam radiation have shown a therapeutic advantage over each modality alone. The purpose of these works is to evaluate the potential of targeted delivery of high LET radiation to the tumor microenvironment via an immune checkpoint inhibitor. METHODS: The impact of protein concentration on the distribution of (111)In-DTPA-anti-PD-L1-BC, an (111)In-antibody conjugate targeted to PD-L1, was evaluated in an immunocompetent mouse model of breast cancer...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28697066/viral-induced-modulation-of-multiple-checkpoint-proteins-in-cancers
#2
Gerard J Nuovo, Virginia A Folcik, Cynthia Magro
Therapy with checkpoint inhibitors represents a major advance in cancer treatment. The purpose of this study was to examine the expression patterns of the checkpoint proteins programmed death ligand 1 (PD L1), PD L2, indoleamine 2,3-dioxygenase 1 (IDO1), and cytotoxic T-lymphocyte antigen 4 (CTLA4) in cancers including those associated with viral infections. Normal, noninflamed tissues rarely express checkpoint proteins with exceptions including the placenta and stomach. Expression of PD L1 was noted in 30%, PD L2 in 18%, IDO1 in 13%, and CTLA4 in 14% of 333 nonviral malignancies including endometrial, ovarian, lung, and breast cancers...
July 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28680745/vaccination-targeting-human-her3-alters-the-phenotype-of-infiltrating-t-cells-and-responses-to-immune-checkpoint-inhibition
#3
Takuya Osada, Michael A Morse, Amy Hobeika, Marcio A Diniz, William R Gwin, Zachary Hartman, Junping Wei, Hongtao Guo, Xiao-Yi Yang, Cong-Xiao Liu, Kensuke Kaneko, Gloria Broadwater, H Kim Lyerly
Expression of human epidermal growth factor family member 3 (HER3), a critical heterodimerization partner with EGFR and HER2, promotes more aggressive biology in breast and other epithelial malignancies. As such, inhibiting HER3 could have broad applicability to the treatment of EGFR- and HER2-driven tumors. Although lack of a functional kinase domain limits the use of receptor tyrosine kinase inhibitors, HER3 contains antigenic targets for T cells and antibodies. Using novel human HER3 transgenic mouse models of breast cancer, we demonstrate that immunization with recombinant adenoviral vectors encoding full length human HER3 (Ad-HER3-FL) induces HER3-specific T cells and antibodies, alters the T cell infiltrate in tumors, and influences responses to immune checkpoint inhibitions...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28652380/immune-escape-in-breast-cancer-during-in-situ-to-invasive-carcinoma-transition
#4
Carlos R Gil Del Alcazar, Sung Jin Huh, Muhammad B Ekram, Anne Trinh, Lin L Liu, Francisco Beca, Xiaoyuan Zi, Minsuk Kwak, Helga Bergholtz, Ying Su, Lina Ding, Hege G Russnes, Andrea L Richardson, Kirsten Babski, Elizabeth Min Hui Kim, Charles McDonnell, Jon Wagner, Ron Rowberry, Gordon J Freeman, Deborah Dillon, Therese Sorlie, Lisa M Coussens, Judy E Garber, Rong Fan, Kristie Bobolis, D Craig Allred, Joon Jeong, So Yeon Park, Franziska Michor, Kornelia Polyak
To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma in situ (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45+CD3+ T cells demonstrated a decrease in CD8+ signatures in IDCs. Immunofluorescence analysis showed fewer activated GZMB+CD8+ T cells in IDC than in DCIS, including in matched DCIS recurrent IDC...
June 26, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28651116/pd-1-pd-l1-and-ctla-4-in-pregnancy-related-and-in-early-onset-breast-cancer-a-comparative-study
#5
Balázs Ács, Lilla Madaras, Anna-Mária Tőkés, Attila Kristóf Kovács, Erzsébet Kovács, Magdolna Ozsvári-Vidákovich, Ádám Karászi, Ede Birtalan, Magdolna Dank, Attila Marcell Szász, Janina Kulka
PURPOSE: We aimed to compare the immunohistochemical expression of PD-1, PD-L1 and CTLA-4 of pregnancy-related breast cancer (PRBC) and early onset non-PRBC (YWBC), and their prognosis prediction potential was correlated to that of conventional clinicopathological factors. METHODS: Twenty-one PRBC cases were paired with 21 YWBC in this matched case-control study. Immune-checkpoint markers (ICM) were evaluated with immunohistochemistry (IHC) on whole slides using the following antibodies: PD-1 (NAT-105), PD-L1 (28-8) and CTLA-4 (F-8)...
June 23, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28624814/pd-l1-and-intratumoral-immune-response-in-breast-cancer
#6
Zhi-Qiang Wang, Katy Milne, Heather Derocher, John R Webb, Brad H Nelson, Peter H Watson
PURPOSE: PD-L1 is thought to play an important role in the antitumor immune response. In this study, we investigated the expression of PD-L1 within breast tumor subsets to better define its prognostic significance. METHODS: Immunohistochemistry was performed to determine PD-L1 tumor cell expression and to enumerate CD8, CD4 and CD68 tumor-infiltrating leucocytes (TIL) in a cohort of 443 breast cancers categorized by molecular subtype. RESULTS: Across the entire cohort, PD-L1 tumor cell expression was observed in 73/443 (16...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28614911/pd-l1-promotes-oct4-and-nanog-expression-in-breast-cancer-stem-cells-by-sustaining-pi3k-akt-pathway-activation
#7
Sheema Almozyan, Dilek Colak, Fatmah Mansour, Ayodele Alaiya, Olfat Al-Harazi, Amal Qattan, Falah Al-Mohanna, Monther Al-Alwan, Hazem Ghebeh
The expression of PD-L1 in breast cancer is associated with estrogen receptor negativity, chemoresistance, and epithelial-to-mesenchymal transition (EMT); all of which are common features of a highly tumorigenic subpopulation of cancer cells termed cancer stem cells (CSCs). Hitherto, the expression and intrinsic role of PD-L1 in the dynamics of breast CSCs has not been investigated. To address this issue, we used transcriptomic datasets, proteomics and several in vitro and in vivo assays. Expression profiling of a large breast cancer dataset (530 patients) showed statistically significant correlation (p<0...
June 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28611201/relationship-of-the-breast-ductal-carcinoma-in-situ-immune-microenvironment-with-clinico-pathological-and-genetic-features
#8
Shona Hendry, Jia-Min B Pang, David Byrne, Sunil R Lakhani, Margaret C Cummings, Ian G Campbell, G Bruce Mann, Kylie L Gorringe, Stephen B Fox
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. <br /><br />Experimental Design: We quantified tumour associated lymphocytes (TILs) 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=55) and mutation data (n=20). <br /><br />Results: TILs were identified in the stroma surrounding DCIS (119/138, 86%) and present at a median TIL score of 5% (range 0-90%)...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28579282/a-radiosensitivity-gene-signature-and-pd-l1-status-predict-clinical-outcome-of-patients-with-invasive-breast-carcinoma-in-the-cancer-genome-atlas-tcga-dataset
#9
Bum-Sup Jang, In Ah Kim
BACKGROUND AND PURPOSE: We investigated the link between the radiosensitivity gene signature and programmed cell death ligand 1 (PD-L1) status and clinical outcome in order to identify a group of patients that would possibly receive clinical benefit of radiotherapy (RT) combined with anti-PD1/PD-L1 therapy. MATERIAL AND METHODS: We validated the identified gene signature related to radiosensitivity and analyzed the PD-L1 status of invasive breast cancer in The Cancer Genome Atlas (TCGA) dataset...
June 1, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28577052/-analysis-of-therapy-relevant-receptors-in-bone-marrow-carcinosis-comparison-of-pathological-and-clinical-parameters
#10
G Massenkeil, C Gropp, H Kreipe, K Hussein
BACKGROUND: Bone marrow carcinosis is a sign of advanced tumor stage with nonspecific clinical and hematological symptoms. Diagnosis is based on bone marrow biopsy and histopathology, but biopsies are not part of the standard work-up in oncological diseases and data on the correlation between clinical presentation and pathological findings are sparse. MATERIAL AND METHODS: In a retrospective single-center study, data from 20 tumor patients with bone marrow carcinosis were analyzed...
July 2017: Der Pathologe
https://www.readbyqxmd.com/read/28572258/immunotherapy-for-breast-cancer-what-are-we-missing
#11
EDITORIAL
Robert H Vonderheide, Susan M Domchek, Amy S Clark
The recent demonstration of modest single-agent activity of programmed death-ligand 1 (PD-L1) and programmed death receptor-1 (PD-1) antibodies in patients with breast cancer has generated hope that breast cancer can be made amenable to immunotherapy. Depending on the subtype of breast cancer, it is now clear in both primary and metastatic disease that the extent of tumor-infiltrating T cells is not only prognostic for survival but predictive of response to nonimmune, standard therapies. Despite these findings, immune cytolytic activity in spontaneous breast tumors, the burden of nonsynonymous tumor mutations, and the predicted load of neoepitopes-factors linked to response to checkpoint blockade in other malignancies-are all relatively modest in breast cancer compared with melanoma or lung cancer...
June 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28537889/immune-signature-of-metastatic-breast-cancer-identifying-predictive-markers-of-immunotherapy-response
#12
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
#13
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
#14
REVIEW
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
#15
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...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28453554/prognostic-value-of-pd-l1-expression-in-tumor-infiltrating-immune-cells-in-cancers-a-meta-analysis
#16
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
#17
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
#18
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
#19
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
#20
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
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