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https://www.readbyqxmd.com/read/29325268/-clinical-significance-of-targeting-drug-based-molecular-biomarkers-expression-in-ovarian-clear-cell-carcinoma
#1
M J Li, H R Li, X Cheng, R Bi, X Y Tu, F Liu, L H Chen
Objective: To assess the expression level of targeting drug-based molecular biomarkers in ovarian clear cell carcinoma (OCCC) tissues and its clinical significance. Methods: A total of 63 OCCC patients included 40 primary OCCC and 23 recurrent OCCC for secondary cytoreductive surgery (SCS), who had received primary surgeries at Fudan University Shanghai Cancer Center between January, 2008 and December, 2015 were enrolled, and immunohistochemistry SP method was used to test human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), BRCA2 and programmed death-ligand 1 (PD-L1)protein expression in paraffin-embedded tissues...
December 25, 2017: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/29299156/inhibition-of-pi4k-iii%C3%AE-radiosensitizes-in-human-tumor-xenograft-and-immune-competent-syngeneic-murine-tumor-model
#2
Younghee Park, Ji Min Park, Dan Hyo Kim, Jeanny Kwon, In Ah Kim
Phosphatidylinositol (PI) 4-kinase (PI4K) has emerged as a potential target for anti-cancer treatment. We recently reported that simeprevir, an anti-hepatitis C viral (HCV) agent, radiosensitized diverse human cancer cells by inhibiting PI4K IIIα in vitro. In this study, we investigated the radiosensitizing effect of simeprevir in an in vivo tumor xenograft model and the mechanism of its interaction. The immune modulatory effect of PI4K IIIα was evaluated in an immune-competent syngeneic murine tumor model...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29287242/checkpoint-inhibitors-in-breast-cancer-current-status
#3
REVIEW
Anne Polk, Inge-Marie Svane, Michael Andersson, Dorte Nielsen
INTRODUCTION: An increasing number of compounds directed against immune checkpoints are currently under clinical development. In this review we summarize current research in breast cancer. MATERIAL AND METHODS: A computer-based literature search was carried out using PubMed and EMBASE; data reported at international meetings and clinicaltrials.gov were included as well. RESULTS: The obtained overall response rate of PD-1/PD-L1 monotherapy varied from 5 to 30% in heavily pretreated triple negative breast cancer (TNBC)...
December 14, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29282694/immune-checkpoint-blockade-in-breast-cancer-therapy
#4
Xia Bu, Yihui Yao, Xiaoyu Li
Cancer immunotherapy is emerging as the most promising novel strategy for cancer treatment. Cancer immunotherapy is broadly categorized into three forms: immune checkpoint modulation, adoptive cell transfer, and cancer vaccine. Immune checkpoint blockade is demonstrated as the most clinically effective treatment with low immune-related adverse events (irAE). Blockade of PD-1/PD-L1 and CTLA-4 has achieved remarkable success in treating various types of tumors, which sparks great interests in this therapeutic strategy and expands the role of immune checkpoint blockade in treating tumors including breast cancer...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29245948/pd-1-pd-l1-interaction-up-regulates-mdr1-p-gp-expression-in-breast-cancer-cells-via-pi3k-akt-and-mapk-erk-pathways
#5
Shengwei Liu, Shuang Chen, Weiguang Yuan, Hongyan Wang, Kewang Chen, Dianjun Li, Dalin Li
Programmed cell death ligand 1 (PD-L1) is an immunosuppressive molecule expressed on tumor cells. By interacting with programmed cell death-1 (PD-1) on T cells, it inhibits immune responses. Because PD-L1 expression on cancer cells increases their chemoresistance, we investigated the correlation between PD-L1 and multidrug resistance 1/ P-glycoprotein (MDR1/P-gp) expression in breast cancer cells. Analysis of breast cancer tissues using tissue microarrays revealed a significant correlation between PD-L1 and MDR1/P-gp protein levels...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29224274/-correlation-analysis-of-pd-l1-expression-and-prognosis-in-triple-negative-breast-cancers
#6
B J Pan, C Xu, G Q Ping, G X Song, W M Zhang, C Wang, Z H Zhang
Objective: To investigate the relationship between PD-L1 expression and the clinicopathologic features and prognosis in triple-negative breast carcinomas (TNBC). Methods: All 142 cases of TNBC were collected from the First Affiliated Hospital of Nanjing Medical University from February 2011 to December 2014, and the surgical excision or biopsy specimens from patients without chemotherapy and radiotherapy were included. Histopathologic analysis of stromal tumor infiltrating lymphocyte (sTIL) was performed on HE sections, and PD-L1 immunohistochemical staining was done with MaxVision...
December 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29212506/chromosome-9p-copy-number-gains-involving-pd-l1-are-associated-with-a-specific-proliferation-and-immune-modulating-gene-expression-program-active-across-major-cancer-types
#7
Jan Budczies, Carsten Denkert, Balázs Győrffy, Peter Schirmacher, Albrecht Stenzinger
BACKGROUND: Inhibition of the PD-L1/PD-1 immune checkpoint axis represents one of the most promising approaches of immunotherapy for various cancer types. However, immune checkpoint inhibition is successful only in subpopulations of patients emphasizing the need for powerful biomarkers that adequately reflect the complex interaction between the tumor and the immune system. Recently, recurrent copy number gains (CNG) in chromosome 9p involving PD-L1 were detected in many cancer types including lung cancer, melanoma, bladder cancer, head and neck cancer, cervical cancer, soft tissue sarcoma, prostate cancer, gastric cancer, ovarian cancer, and triple-negative breast cancer...
December 6, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/29209569/resistance-to-her2-targeted-anti-cancer-drugs-is-associated-with-immune-evasion-in-cancer-cells-and-their-derived-extracellular-vesicles
#8
Vanesa G Martinez, Sadhbh O'Neill, Josephine Salimu, Susan Breslin, Aled Clayton, John Crown, Lorraine O'Driscoll
Neuromedin U (NmU) -a neuropeptide belonging to the neuromedin family- plays a substantial role in HER2-positive breast cancer, correlating with increased aggressiveness, resistance to HER2-targeted therapies and overall significantly poorer outcome for patients. However, the mechanism through which it exerts these effects remains unclear. To elucidate this, initially we used HER2-positive breast cancer cells stably over-expressing NmU. These cells and their released extracellular vesicles (EVs) had increased amounts of the immunosuppressive cytokine TGFβ1 and the lymphocyte activation inhibitor PD-L1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29198959/evaluation-of-immune-reaction-and-pd-l1-expression-using-multiplex-immunohistochemistry-in-her2-positive-breast-cancer-the-association-with-response-to-anti-her2-neoadjuvant-therapy
#9
Yanjun Hou, Hiroaki Nitta, Lai Wei, Peter M Banks, Anil V Parwani, Zaibo Li
BACKGROUND: Immune reaction with tumor-infiltrating lymphocytes (TILs) has been extensively investigated in breast cancer. Programmed cell death 1 and its ligand (PD-L1) are key physiologic suppressors of cytotoxic immune reaction. However, the combination of TILs with PD-L1 expression has not been well studied in breast cancer. PATIENTS AND METHODS: A multi-color immunohistochemical multiplex assay simultaneously detecting PD-L1, CD8, and CD163 was performed on biopsy whole sections from 123 HER2-positive (HER2+) breast cancers, including 64 treated with anti-HER2 neoadjuvant therapy and subsequent resection...
November 9, 2017: Clinical Breast Cancer
https://www.readbyqxmd.com/read/29168430/triple-negative-breast-cancer-prognostic-role-of-immune-related-factors-a-systematic-review
#10
Elisabeth Specht Stovgaard, Dorte Nielsen, Estrid Hogdall, Eva Balslev
PURPOSE: Treatment of breast cancer has been increasingly successful in recent years with the advent of HER2-receptor targeted treatment and endocrine treatment. However, the triple negative subgroup of breast cancer (TNBC) (estrogen-, progesterone- and HER2-receptor negative) still lacks targeted treatment options. TNBC is a type of breast cancer that often affects younger women, and generally has a worse prognosis than other types of breast cancer. Recently, the complex role of the immune system in cancer growth, elimination and metastasis has been the object of increased attention...
November 23, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29163540/local-high-dose-radiotherapy-induces-systemic-immunomodulating-effects-of-potential-therapeutic-relevance-in-oligometastatic-breast-cancer
#11
Elena Muraro, Carlo Furlan, Michele Avanzo, Debora Martorelli, Elisa Comaro, Aurora Rizzo, Damiana A Fae', Massimiliano Berretta, Loredana Militello, Alessandro Del Conte, Simon Spazzapan, Riccardo Dolcetti, Marco Trovo'
Local irradiation of cancer through radiotherapy can induce spontaneous regression of non-directly irradiated lesions, suggesting the involvement of systemic antitumor immune responses. In oligometastatic breast cancer (BC) patients, the use of stereotactic body radiotherapy (SBRT) favors the local control of treated lesions and may contribute to break local tolerance and release tumor-associated antigens (TAAs), improving host antitumor immunity. We performed a detailed immunomonitoring of BC patients undergoing SBRT to verify its ability to "switch on" the anti-tumor immunity both systemically, in peripheral blood, and locally, employing in vitro BC models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163490/immune-checkpoint-molecules-on-tumor-infiltrating-lymphocytes-and-their-association-with-tertiary-lymphoid-structures-in-human-breast-cancer
#12
Cinzia Solinas, Soizic Garaud, Pushpamali De Silva, Anaïs Boisson, Gert Van den Eynden, Alexandre de Wind, Paolo Risso, Joel Rodrigues Vitória, François Richard, Edoardo Migliori, Grégory Noël, Hugues Duvillier, Ligia Craciun, Isabelle Veys, Ahmad Awada, Vincent Detours, Denis Larsimont, Martine Piccart-Gebhart, Karen Willard-Gallo
There is an exponentially growing interest in targeting immune checkpoint molecules in breast cancer (BC), particularly in the triple-negative subtype where unmet treatment needs remain. This study was designed to analyze the expression, localization, and prognostic role of PD-1, PD-L1, PD-L2, CTLA-4, LAG3, and TIM3 in primary BC. Gene expression analysis using the METABRIC microarray dataset found that all six immune checkpoint molecules are highly expressed in basal-like and HER2-enriched compared to the other BC molecular subtypes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29137398/prognostic-significance-of-pd-l1-expression-and-tumor-infiltrating-lymphocyte-in-surgically-resectable-non-small-cell-lung-cancer
#13
Gen Lin, Xirong Fan, Weifeng Zhu, Cheng Huang, Wu Zhuang, Haipeng Xu, Xiandong Lin, Dan Hu, Yunjian Huang, Kan Jiang, Qian Miao, Chao Li
Programmed death ligand 1 (PD-L1) expression is a predictive biomarker of the success of PD-1/PD-L1 inhibitor therapy for patients with advanced non-small cell lung cancer (NSCLC) but its role as a prognostic marker for early stage resectable NSCLC remains unclear. Here, we studied PD-L1 expression and tumor infiltrating lymphocytes (TILs) in surgically resectable NSCLC and correlate the finding with clinicopathological features and patient outcomes. Total of 170 archival samples of resectable NSCLC were probed for PD-L1 expression using the clone 22C3 pharmDx kit...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29135534/the-multiple-faces-of-programmed-cell-death-ligand-1-expression-in-malignant-and-nonmalignant-cells
#14
Edwin R Parra, Pamela Villalobos, Jaime Rodriguez-Canales
Preliminary data suggest that tumor expression of programmed cell death ligand 1 (PD-L1) protein in human cancers, as determined by immunohistochemistry in formalin-fixed, paraffin-embedded tissue samples, may predict clinical response to anti-PD-1/PD-L1 therapy. PD-L1 is not a specific tumor marker and its expression is also observed in various nonmalignant cells, such as macrophages and lymphocytes, causing confusion in immunohistochemistry analysis when these inflammatory cells are overlapping with tumors cells...
November 13, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29129094/rational-combination-of-immunotherapy-for-triple-negative-breast-cancer-treatment
#15
Chia-Wei Li, Seung-Oe Lim, Jennifer L Hsu, Mien-Chie Hung
Recent evidence indicates that tumor infiltrating lymphocytes (TILs), including cytotoxic T cells, are present in the tumor microenvironment of triple-negative breast cancers (TNBC). Despite the presence of cytotoxic T cells, these tumors still develop, progress, and metastasize, suggesting evasion of immune response. One mechanism of immunosuppression is the presence of the T cell inhibitory molecule, programmed death protein 1 (PD-1), on infiltrating T cells and its cognate ligand programmed death ligand 1 (PD-L1) on tumor cells, myeloid dendritic cells (DCs), and macrophages, in the tumor microenvironment...
October 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29126881/triple-negative-breast-cancer-key-role-of-tumor-associated-macrophages-in-regulating-the-activity-of-anti-pd-1-pd-l1-agents
#16
REVIEW
Matteo Santoni, Emanuela Romagnoli, Tiziana Saladino, Laura Foghini, Stefania Guarino, Marco Capponi, Massimo Giannini, Paolo Decembrini Cognigni, Gerardo Ferrara, Nicola Battelli
Triple-negative breast cancer (TNBC) is associated with a poor prognosis, due to its aggressive behaviour and lack of effective targeted therapies. Immunocheckpoint inhibitors, such as anti-programmed cell death 1 (PD-1) and anti-PD-ligand(L)1 agents, are in course of investigation in TNBC, used alone or in combination with other systemic or local approaches. However, the high cost of these drugs and the lack of validated predictive biomarkers support the development of strategies aimed to overcome resistance and optimize the efficacy of these approaches...
November 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29118259/matrix-binding-checkpoint-immunotherapies-enhance-antitumor-efficacy-and-reduce-adverse-events
#17
Jun Ishihara, Kazuto Fukunaga, Ako Ishihara, Hans M Larsson, Lambert Potin, Peyman Hosseinchi, Gabriele Galliverti, Melody A Swartz, Jeffrey A Hubbell
Immune checkpoint blockade exhibits considerable antitumor activity, but previous studies have reported instances of severe treatment-related adverse events. We sought to explore local immune checkpoint blockade, with an antibody (Ab) form that would be retained intra- or peritumorally, limiting systemic exposure. To accomplish this, we conjugated the checkpoint blockade Abs to an extracellular matrix (ECM)-super-affinity peptide derived from placenta growth factor-2 (PlGF-2123-144). We show enhanced tissue retention and lower Ab concentrations in blood plasma after PlGF-2123-144 conjugation, reducing systemic side effects such as the risk of autoimmune diabetes...
November 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29117944/small-molecule-sigma1-modulator-induces-autophagic-degradation-of-pd-l1
#18
Christina M Maher, Jeffrey D Thomas, Derick A Haas, Charles G Longen, Halley M Oyer, Jane Y Tong, Felix J Kim
Emerging evidence suggests that Sigma1 (SIGMAR1, also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis. Previously, we demonstrated that some small molecule modulators of Sigma1 alter endoplasmic reticulum (ER) associated protein homeostasis pathways in cancer cells, including the unfolded protein response and autophagy. Programmed death-ligand 1 (PD-L1) is a type 1 integral membrane glycoprotein that is co-translationally inserted into the ER and is processed and transported through the secretory pathway...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29104508/high-pd-l1-expression-is-closely-associated-with-tumor-infiltrating-lymphocytes-and-leads-to-good-clinical-outcomes-in-chinese-triple-negative-breast-cancer-patients
#19
NiJiati AiErken, Hui-Juan Shi, Yu Zhou, Nan Shao, Jin Zhang, Yawei Shi, Zhong-Yu Yuan, Ying Lin
BACKGROUND: To investigate the role of Programmed death ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in tumor recurrence and metastasis of Chinese patients suffering from triple negative breast cancer (TNBC). METHODS: PD-L1 immunohistochemistry was performed on 215 TNBCs. Also, the prevalence of TILs correlated the expression of PD-L1 and TILs with clinical outcomes. Kaplan-Meier and the model analyses of univariate Cox proportional hazards were utilized to compare the survival of patients with positive PD-L1 expression with those with negative PD-L1 expression...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/29093678/immune-related-adverse-events-associated-with-anti-pd-1-pd-l1-treatment-for-malignancies-a-meta-analysis
#20
Peng-Fei Wang, Yang Chen, Si-Ying Song, Ting-Jian Wang, Wen-Jun Ji, Shou-Wei Li, Ning Liu, Chang-Xiang Yan
Background: Treatment of cancers with programmed cell death protein 1 (PD-1) pathway inhibitors can lead to immune-related adverse events (irAEs), which could be serious and even fetal. Therefore, clinicians should be aware of the characteristics of irAEs associated with the use of such drugs. Methods: The MEDLINE, EMBASE, and Cochrane databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1 treatment; irAEs; and cancer. R© package Meta was used to pool incidence. Results: Forty-six studies representing 12,808 oncologic patients treated with anti-PD-1/PD-L1 agents were included in the meta-analysis...
2017: Frontiers in Pharmacology
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