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Pd-l1 breast cancer

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https://www.readbyqxmd.com/read/29789418/juxtacrine-signaling-inhibits-antitumor-immunity-by-upregulating-pd-l1-expression
#1
Wen-Hao Yang, Jong-Ho Cha, Weiya Xia, Heng-Huan Lee, Li-Chuan Chan, Ying-Nai Wang, Jennifer L Hsu, Guoxin Ren, Mien-Chie Hung
Programmed death-ligand 1 (PD-L1) is a well-known immune checkpoint protein that helps cancer cells evade immune response. Anti-PD-L1 immune therapy has been approved for the treatment of several advanced human cancers. Therefore, further understanding of the regulatory mechanisms of PD-L1 is critical to improve PD-L1-targeting immunotherapy. Recent studies indicated that contact-dependent pathways may regulate anticancer immunity, highlighting the importance of cell contact-induced signaling in cancer immunity...
May 22, 2018: Cancer Research
https://www.readbyqxmd.com/read/29757193/eya3-promotes-breast-tumor-associated-immune-suppression-via-threonine-phosphatase-mediated-pd-l1-upregulation
#2
Rebecca L Vartuli, Hengbo Zhou, Lingdi Zhang, Rani K Powers, Jared Klarquist, Pratyaydipta Rudra, Melanie Y Vincent, Debashis Ghosh, James C Costello, Ross M Kedl, Jill E Slansky, Rui Zhao, Heide L Ford
Eya proteins are critical developmental regulators that are highly expressed in embryogenesis but downregulated after development. Amplification and/or re-expression of Eyas occurs in many tumor types. In breast cancer, Eyas regulate tumor progression by acting as transcriptional cofactors and tyrosine phosphatases. Intriguingly, Eyas harbor a separate threonine (Thr) phosphatase activity, which was previously implicated in innate immunity. Here we describe what we believe to be a novel role for Eya3 in mediating triple-negative breast cancer-associated immune suppression...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29746929/trastuzumab-upregulates-pd-l1-as-a-potential-mechanism-of-trastuzumab-resistance-through-engagement-of-immune-effector-cells-and-stimulation-of-ifn%C3%AE-secretion
#3
Bharat K R Chaganty, Songbo Qiu, Anneliese Gest, Yang Lu, Cristina Ivan, George A Calin, Louis M Weiner, Zhen Fan
Here, we report that treatment of syngeneic mouse tumors transduced to overexpress human epidermal growth factor receptor-2 (HER2) with the anti-human HER2 antibody trastuzumab upregulated the level of programmed death-ligand 1 (PD-L1), an important negative regulator of T-cell response, in a transgenic mouse model immune-tolerant to human HER2. We further found that trastuzumab alone had no detectable effect on the level of PD-L1 expression in monocultures of HER2-overexpressing human breast cancer cells but upregulated PD-L1 in the same panel of HER2-overexpressing breast cancer cells when they were co-cultured with human peripheral blood mononuclear cells, and the upregulation of PD-L1 could be blocked by an IFNγ-neutralizing antibody...
May 7, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29721396/m7824-a-novel-bifunctional-anti-pd-l1-tgf%C3%AE-trap-fusion-protein-promotes-anti-tumor-efficacy-as-monotherapy-and-in-combination-with-vaccine
#4
Karin M Knudson, Kristin C Hicks, Xiaoling Luo, Jin-Qiu Chen, Jeffrey Schlom, Sofia R Gameiro
Tumors evade host immune surveillance through multiple mechanisms, including the generation of a tumor microenvironment that suppresses immune effector function. Secretion of TGFβ and upregulation of immune checkpoint programmed cell death ligand-1 (PD-L1) are two main contributors to immune evasion and tumor progression. Here, we examined the efficacy of a first-in-class bifunctional checkpoint inhibitor, the fusion protein M7824, comprising the extracellular domain of human TGFβRII (TGFβ Trap) linked to the C-terminus of human anti-PD-L1 heavy chain (αPD-L1)...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29719817/the-role-of-epstein-barr-virus-in-cervical-cancer-a-brief-update
#5
REVIEW
Semir Vranic, Farhan Sachal Cyprian, Saghir Akhtar, Ala-Eddin Al Moustafa
Epstein-Barr virus (EBV) belongs to the group of gamma-herpes viruses and was the first recognized human oncovirus. EBV is responsible for infectious mononucleosis and multiple lymphoid and epithelial malignancies including B-cell lymphomas (Burkitt lymphoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disorder), various T-cell/NK lymphoproliferative disorders, nasopharyngeal carcinoma, and gastric carcinoma, respectively. In addition, the presence of EBV has been documented in other cancers including breast, prostate, oral, and salivary gland carcinomas...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29715119/eribulin-promotes-antitumor-immune-responses-in-patients-with-locally-advanced-or-metastatic-breast-cancer
#6
Wataru Goto, Shinichiro Kashiwagi, Yuka Asano, Koji Takada, Tamami Morisaki, Hisakazu Fujita, Tsutomu Takashima, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND/AIM: Several proteins involved in immune regulation and the relationship among these, the tumor microenvironment, and clinical outcomes of eribulin treatment were evaluated in advanced or metastatic breast cancer patients. PATIENTS AND METHODS: This retrospective cohort study comprised 52 eribulin-treated locally advanced or metastatic breast cancer patients. Cancer tissue samples were obtained before and after treatment in 10 patients. Immunohistochemistry was performed to determine programmed death (PD)-1, CD8, and forkhead box P3 (FOXP3) expression by stromal tumor-infiltrating lymphocytes, and PD-ligand (L1) and PD-L2 expression by cancer cells...
May 2018: Anticancer Research
https://www.readbyqxmd.com/read/29707124/-brca1-2-and-tp53-mutation-status-associates-with-pd-1-and-pd-l1-expression-in-ovarian-cancer
#7
Verena Wieser, Inge Gaugg, Martina Fleischer, Giridhar Shivalingaiah, Soeren Wenzel, Susanne Sprung, Sigurd F Lax, Alain G Zeimet, Heidelinde Fiegl, Christian Marth
Checkpoint molecules such as programmed cell death protein-1 (PD-1) and its ligand PD-L1 are critically required for tumor immune escape. The objective of this study was to investigate tumoral PD-1 and PD-L1 mRNA-expression in a cohort of ovarian cancer (OC) patients in relation to tumor mutations. We analyzed mRNA expression of PD-1 , PD-L1 and IFNG by quantitative real-time PCR in tissue of 170 patients with low grade-serous (LGSOC), high-grade serous (HGSOC), endometrioid and clear cell OC compared to 28 non-diseased tissues (ovaries and fallopian tubes) in relation to tumor protein 53 ( TP53 ) and breast cancer gene 1/2 ( BRCA1/2 ) mutation status...
April 3, 2018: Oncotarget
https://www.readbyqxmd.com/read/29702007/dual-inhibition-of-stat1-and-stat3-activation-downregulates-expression-of-pd-l1-in-human-breast-cancer-cells
#8
Varun Sasidharan Nair, Salman M Toor, Bassam R Ali, Eyad Elkord
OBJECTIVES: Breast cancer is the most commonly diagnosed cancer, and it is a leading cause of cancer-related deaths in females worldwide. Triple-negative breast cancer (TNBC) constitutes 15% of breast cancer and shows distinct metastasis profiles with poor prognosis. Strong PD-L1 expression has been observed in some tumors, supporting their escape from immune surveillance. Targeting PD-L1 could be a promising therapeutic approach in breast cancer patients. We investigated potential molecular mechanisms for constitutive expression of PD-L1 by inhibiting upstream STAT1 and STAT3 signals...
April 27, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29695766/vinorelbine-cyclophosphamide-and-5-fu-effects-on-the-circulating-and-intratumoural-landscape-of-immune-cells-improve-anti-pd-l1-efficacy-in-preclinical-models-of-breast-cancer-and-lymphoma
#9
Stefania Orecchioni, Giovanna Talarico, Valentina Labanca, Angelica Calleri, Patrizia Mancuso, Francesco Bertolini
BACKGROUND: Anti-PD-1 and anti-PD-L1 checkpoint inhibitors (CIs) are clinically active in many types of cancer. However, only a minority of patients achieve a complete and/or long-lasting clinical response. We studied the effects of different doses of three widely used, orally active chemotherapeutics (vinorelbine, cyclophosphamide and 5-FU) over local and metastatic tumour growth, and the landscape of circulating and tumour-infiltrating immune cells involved in CI activity. METHODS: Immunocompetent Balb/c mice were used to generate models of breast cancer (BC) and B-cell lymphoma...
April 26, 2018: British Journal of Cancer
https://www.readbyqxmd.com/read/29690797/atezolizumab-for-the-treatment-of-breast-cancer
#10
Debora Basile, Giacomo Pelizzari, Maria Grazia Vitale, Camilla Lisanti, Marika Cinausero, Donatella Iacono, Fabio Puglisi
Breast cancer (BC) is the most common cancer diagnosed among women. The development of new personalized therapeutic strategies has reshaped the landscape in this field. However, BC is still the first cause of death among women. Interestingly, several preclinical studies and some clinical evidences are focused their attention on the role of immune system and immunotherapy on cancer control, also in BC. Areas covered: Usually, BC has been considered a not immunogenic tumor for its low mutational load. However, recent studies have evidenced that some subtypes, triple negative and HER-2 positive BC, are "hot" tumors, thus more immunogenic...
April 24, 2018: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29679564/frequencies-and-expression-levels-of-programmed-death-ligand-1-pd-l1-in-circulating-tumor-rna-ctrna-in-various-cancer-types
#11
Toshiyuki Ishiba, Andreas-Claudius Hoffmann, Joshua Usher, Yahya Elshimali, Todd Sturdevant, Mai Dang, Yolanda Jaimes, Rama Tyagi, Ronald Gonzales, Mary Grino, Jacek K Pinski, Afsaneh Barzi, Luis E Raez, Wilfried E Eberhardt, Dirk Theegarten, Heinz-Josef Lenz, Hiroyuki Uetake, Peter V Danenberg, Kathleen Danenberg
BACKGROUND: Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, provides information about relative expression levels of important genes. In this study, we analyzed PD-L1 expression in ctRNA isolated from various cancer types...
April 27, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29675979/senescent-cells-re-engineered-to-express-spd-1-for-inhibiting-pd-1-pd-l1-as-a-vaccination-approach-against-breast-cancer
#12
Zehong Chen, Kang Hu, Lieting Feng, Ruxiong Su, Nan Lai, Zike Yang, Shijun Kang
Various types of vaccines have been proposed as approaches for prevention or delay of the onset of cancer by boosting the endogenous immune system. We previously developed a senescent-cell-based vaccine, induced by radiation and veliparib, as a preventive and therapeutic tool against triple-negative breast cancer. However, the PD-1/PD-L1 pathway was found to play an important role in vaccine failure. Hence, we further developed sPD1-expressing senescent cells to overcome PD-L1/PD1-mediated immune suppression while vaccinating to promote dendritic cells (DCs) maturity, thereby amplifying T cell activation...
April 20, 2018: Cancer Science
https://www.readbyqxmd.com/read/29672601/expression-of-immune-checkpoint-regulators-cytotoxic-t-lymphocyte-antigen-4-ctla-4-and-programmed-death-ligand-1-pd-l1-in-female-breast-carcinomas
#13
Ari Kassardjian, Peter I Shintaku, Neda A Moatamed
BACKGROUND: Immune checkpoint regulators, cytotoxic T lymphocyte antigen 4 (CTLA-4) and the programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) have emerged as promising new targets for cancer therapeutics. While tumor expression of PD-L1 has been shown to have objective responses to anti-PD-L1 immunotherapies, the clinical implications of CTLA-4 expression in tumor cells or immune cells in the tumor microenvironment is still controversial. We investigated the expression of CTLA-4 and PD-L1 in human breast tumors and provided a scoring system for the systematic evaluation of CTLA-4 staining...
2018: PloS One
https://www.readbyqxmd.com/read/29644338/hypothesis-can-the-abscopal-effect-explain-the-impact-of-adjuvant-radiotherapy-on-breast-cancer-mortality
#14
REVIEW
Ismail Jatoi, John R Benson, Ian Kunkler
Radiotherapy is an integral component of loco-regional therapy for breast cancer. Randomized controlled trials indicate that increasing the extent of extirpative surgery primarily reduces the risk of local recurrences, while the addition of radiotherapy to surgery can also reduce the risk of distant recurrences, thereby lowering breast cancer-specific mortality. This may suggest an "abscopal" effect beyond the immediate zone of loco-regional irradiation that favorably perturbs the natural history of distant micrometastases...
2018: NPJ Breast Cancer
https://www.readbyqxmd.com/read/29615305/early-stage-her2-positive-breast-cancers-not-achieving-a-pcr-from-neoadjuvant-trastuzumab-or-pertuzumab-based-regimens-have-an-immunosuppressive-phenotype
#15
Jeremy Force, Lynn J Howie, Sara E Abbott, Rex Bentley, P Kelly Marcom, Gretchen Kimmick, Kelly Westbrook, Sarah L Sammons, Michelle Parks, Donna L Topping, Ryan Emerson, Gloria Broadwater, Terry Hyslop, Kimberly L Blackwell, Smita K Nair
BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) might predict pathologic complete response (pCR) in patients with HER2-positive (HER2+ ) breast cancer treated with trastuzumab (H). Docetaxel (T), carboplatin (C), H, and pertuzumab (P) have immune-modulating effects. Pre- and post-treatment immune biomarkers in cancers treated with neoadjuvant TCH with or without P are lacking. In this study we quantified baseline and changes in TILs, cluster of differentiation (CD) 4+ , CD8+ , FoxP3+ , and PD-L1+ cells using immunohistochemistry (IHC) and quantified productive T-cell receptor β (TCRβ) rearrangements and TCRβ clonality using next-generation sequencing (NGS) in 30 HER2+ breast cancer tissues treated with neoadjuvant H with or without P regimens...
February 24, 2018: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29615076/use-of-the-tumor-infiltrating-cd8-to-foxp3-lymphocyte-ratio-in-predicting-treatment-responses-to-combination-therapy-with-pertuzumab-trastuzumab-and-docetaxel-for-advanced-her2-positive-breast-cancer
#16
Koji Takada, Shinichiro Kashiwagi, Wataru Goto, Yuka Asano, Katsuyuki Takahashi, Tsutomu Takashima, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: The trastuzumab, pertuzumab, and docetaxel (TPD) regimen is strongly recommended as a treatment option for first-line therapy for advanced human epidermal growth factor receptor (HER) 2-positive breast cancer. Monitoring the host microenvironments in cancer plays a significant role in predicting prognoses and curative effects. It is important to clarify the role of immune related gene expression in tumor-infiltrating lymphocytes in the tumor microenvironment. In this study, we evaluated the impact of chemotherapy with a TPD regimen, on immune micro environments in HER2-positive breast cancer using immune related proteins as indicators...
April 3, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29615063/prediction-of-treatment-responses-to-neoadjuvant-chemotherapy-in-triple-negative-breast-cancer-by-analysis-of-immune-checkpoint-protein-expression
#17
Yuka Asano, Shinichiro Kashiwagi, Wataru Goto, Koji Takada, Katsuyuki Takahashi, Tamami Morisaki, Hisakazu Fujita, Tsutomu Takashima, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: "Avoiding immune destruction" has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell death-ligand (PD-L) 1 pathway is an important immunosuppression mechanism that allows cancer cells to escape host immunity. The present study investigated how the expressions of these immune checkpoint proteins affected responses to neo-adjuvant chemotherapy (NAC) in breast cancer. METHODS: A total of 177 patients with resectable early-stage breast cancer were treated with NAC...
April 4, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29596308/ep4-as-a-therapeutic-target-for-aggressive-human-breast-cancer
#18
REVIEW
Mousumi Majumder, Pinki Nandi, Ahmed Omar, Kingsley Chukwunonso Ugwuagbo, Peeyush K Lala
G-protein-coupled receptors (GPCRs, also called seven-transmembrane or heptahelical receptors) are a superfamily of cell surface receptor proteins that bind to many extracellular ligands and transmit signals to an intracellular guanine nucleotide-binding protein (G-protein). When a ligand binds, the receptor activates the attached G-protein by causing the exchange of Guanosine-5'-triphosphate (GTP) for guanosine diphosphate (GDP). They play a major role in many physiological functions, as well as in the pathology of many diseases, including cancer progression and metastasis...
March 29, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29588392/tumor-infiltrating-lymphocytes-and-pd-l1-expression-in-pre-and-post-treatment-breast-cancers-in-the-swog-s0800-phase-ii-neoadjuvant-chemotherapy-trial
#19
Vasiliki Pelekanou, William E Barlow, Zeina Nahleh, Brad Wasserman, Ying-Chun Lo, Marie-Kristin von Wahlde, Daniel F Hayes, Gabriel N Hortobagyi, Julie R Gralow, Debu Tripathy, Peggy L Porter, Borbala Szekely, Christos Hatzis, David L Rimm, Lajos Pusztai
Our aim was to examine the association of pre-treatment tumor infiltrating lymphocyte (TIL) count and PD-L1 levels with pathologic complete response (pCR) and assess immune marker changes following treatment in tumor specimens from the S0800 clinical trial which randomized patients to bevacizumab+nab-paclitaxel followed by doxorubicin/cyclophosphamide (AC) versus two control arms without bevacizumab (varying sequence of AC and nab-paclitaxel). TILs were assessed in 124 pre- and 62 post-treatment tissues (including 59 pairs)...
March 27, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29581837/molecular-and-clinical-features-of-the-tp53-signature-gene-expression-profile-in-early-stage-breast-cancer
#20
Shigeo Yamaguchi, Shin Takahashi, Kaoru Mogushi, Yuki Izumi, Yumi Nozaki, Tadashi Nomizu, Yoichiro Kakugawa, Takanori Ishida, Noriaki Ohuchi, Chikashi Ishioka, Shunsuke Kato
Purpose: TP53 signature has a robust predictive performance for prognosis in early-stage breast cancer, but the experiment that reported this relied on public microarray data and fresh-frozen samples. Before TP53 signature can be used in a clinical setting, a simple and low-cost diagnostic system using formalin-fixed paraffin-embedded (FFPE) samples is needed. New treatments based on the biological characteristics of TP53 signature are expected to follow. Experimental Design: TP53 signature was evaluated in 174 FFPE early breast cancer specimens using digital quantification via the nCounter technique (NanoString)...
March 6, 2018: Oncotarget
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