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Lieping Chen

Yu Zhang, Lieping Chen
No abstract text is available yet for this article.
August 4, 2016: JAMA Oncology
Kurt A Schalper, Daniel Carvajal-Hausdorf, Joseph McLaughlin, Mehmet Altan, Vamsidhar Velcheti, Patricia Gaule, Miguel F Sanmamed, Lieping Chen, Roy S Herbst, David L Rimm
PURPOSE: To determine the expression level, associations and biological role of PD-L1, IDO-1 and B7-H4 in non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Using multiplexed quantitative immunofluorescence (QIF), we measured the levels of PD-L1, IDO-1, B7-H4 and different tumor infiltrating lymphoycte (TIL) subsets in 552 stages I-IV lung carcinomas from 2 independent populations. Associations between the marker levels, TILs and major clinico-pathological variables were determined...
July 20, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Yuwen Zhu, Sheng Yao, Mathew M Augustine, Haiying Xu, Jun Wang, Jingwei Sun, Megan Broadwater, William Ruff, Liqun Luo, Gefeng Zhu, Koji Tamada, Lieping Chen
The central nervous system (CNS) is an immune-privileged organ with the capacity to prevent excessive inflammation. Aside from the blood-brain barrier, active immunosuppressive mechanisms remain largely unknown. We report that a neuron-specific molecule, synaptic adhesion-like molecule 5 (SALM5), is a crucial contributor to CNS immune privilege. We found that SALM5 suppressed lipopolysaccharide-induced inflammatory responses in the CNS and that a SALM-specific monoclonal antibody promoted inflammation in the CNS, and thereby aggravated clinical symptoms of mouse experimental autoimmune encephalomyelitis...
April 2016: Science Advances
Weiping Zou, Jedd D Wolchok, Lieping Chen
PD-L1 and PD-1 (PD) pathway blockade is a highly promising therapy and has elicited durable antitumor responses and long-term remissions in a subset of patients with a broad spectrum of cancers. How to improve, widen, and predict the clinical response to anti-PD therapy is a central theme in the field of cancer immunology and immunotherapy. Oncologic, immunologic, genetic, and biological studies focused on the human cancer microenvironment have yielded substantial insight into this issue. Here, we focus on tumor microenvironment and evaluate several potential therapeutic response markers including the PD-L1 and PD-1 expression pattern, genetic mutations within cancer cells and neoantigens, cancer epigenetics and effector T cell landscape, and microbiota...
March 2, 2016: Science Translational Medicine
Han Sun, Liqun Luo, Bachchu Lal, Xinrong Ma, Lieping Chen, Christine L Hann, Amy M Fulton, Daniel J Leahy, John Laterra, Min Li
Two-pore domain potassium (K2P) channels act to maintain cell resting membrane potential--a prerequisite for many biological processes. KCNK9, a member of K2P family, is implicated in cancer, owing to its overexpression in human tumours and its ability to promote neoplastic cell survival and growth. However, KCNK9's underlying contributions to malignancy remain elusive due to the absence of specific modulators. Here we describe the development of monoclonal antibodies against the KCNK9 extracellular domain and their functional effects...
February 4, 2016: Nature Communications
Nicolas Jacquelot, María Paula Roberti, David P Enot, Sylvie Rusakiewicz, Michaela Semeraro, Sarah Jégou, Camila Flores, Lieping Chen, Byoung S Kwon, Christophe Borg, Benjamin Weide, François Aubin, Stéphane Dalle, Holbrook Kohrt, Maha Ayyoub, Guido Kroemer, Aurélien Marabelle, Andréa Cavalcanti, Alexander Eggermont, Laurence Zitvogel
Stage III metastatic melanomas require adequate adjuvant immunotherapy to prevent relapses. Prognostic factors are awaited to optimize the clinical management of these patients. The magnitude of metastatic lymph node invasion and the BRAF(V600) activating mutation have clinical significance. Based on a comprehensive immunophenotyping of 252 parameters per patient in paired blood and metastatic lymph nodes performed in 39 metastatic melanomas, we found that blood markers were as contributive as tumor-infiltrated lymphocyte immunotypes, and parameters associated with lymphocyte exhaustion/suppression showed higher clinical significance than those related to activation or lineage...
May 2016: Journal of Investigative Dermatology
Ilseyar Akhmetzyanova, Malgorzata Drabczyk, C Preston Neff, Kathrin Gibbert, Kirsten K Dietze, Tanja Werner, Jia Liu, Lieping Chen, Karl S Lang, Brent E Palmer, Ulf Dittmer, Gennadiy Zelinskyy
No abstract text is available yet for this article.
December 2015: PLoS Pathogens
Hyo Jin Park, Joon Seok Park, Yun Hee Jeong, Jimin Son, Young Ho Ban, Byoung-Hee Lee, Lieping Chen, Jun Chang, Doo Hyun Chung, Inhak Choi, Sang-Jun Ha
No abstract text is available yet for this article.
December 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Ilseyar Akhmetzyanova, Malgorzata Drabczyk, C Preston Neff, Kathrin Gibbert, Kirsten K Dietze, Tanja Werner, Jia Liu, Lieping Chen, Karl S Lang, Brent E Palmer, Ulf Dittmer, Gennadiy Zelinskyy
Cytotoxic CD8+ T Lymphocytes (CTL) efficiently control acute virus infections but can become exhausted when a chronic infection develops. Signaling of the inhibitory receptor PD-1 is an important mechanism for the development of virus-specific CD8+ T cell dysfunction. However, it has recently been shown that during the initial phase of infection virus-specific CD8+ T cells express high levels of PD-1, but are fully competent in producing cytokines and killing virus-infected target cells. To better understand the role of the PD-1 signaling pathway in CD8+ T cell cytotoxicity during acute viral infections we analyzed the expression of the ligand on retrovirus-infected cells targeted by CTLs...
October 2015: PLoS Pathogens
Diya Zhang, Shenglai Li, Lingjing Hu, Lieping Sheng, Lili Chen
BACKGROUND: Protease-activated receptors (PARs) are G-protein-coupled receptors with an active role in mediating inflammation, pain and other functions. The oral pathogen Porphyromonas gingivalis (P. gingivalis) secretes proteases that activate PARs. The aim of this study was to elucidate the role of PARs in the pathogenesis of chronic periodontitis by expression analysis of PARs in human gingival epithelial cells (GECs) before and after P. gingivalis supernatants treatment. METHODS: GECs were isolated from healthy human gingival tissue samples...
2015: BMC Oral Health
Lieping Chen, Xue Han
Major progress has been made toward our understanding of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway (referred to as the PD pathway). mAbs are already being used to block the PD pathway to treat human cancers (anti-PD therapy), especially advanced solid tumors. This therapy is based on principles that were discovered through basic research more than a decade ago, but the great potential of this pathway to treat a broad spectrum of advanced human cancers is just now becoming apparent...
September 2015: Journal of Clinical Investigation
Marina K Baine, Gabriela Turcu, Christopher R Zito, Adebowale J Adeniran, Robert L Camp, Lieping Chen, Harriet M Kluger, Lucia B Jilaveanu
Renal cell carcinoma (RCC) is one of the most chemo- and radio-resistant malignancies, with poor associated patient survival if the disease metastasizes. With recent advances in immunotherapy, particularly with PD-1/PD-L1 blockade, outcomes are improving, but a substantial subset of patients does not respond to the new agents. Identifying such patients and improving the therapeutic ratio has been a challenge, although much effort has been made to study PD-1/PD-L1 status in pre-treatment tumor. However, tumor infiltrating lymphocyte (TIL) content might also be predictive of response, and our goal was to characterize TIL content and PD-L1 expression in RCC tumors from various anatomic sites...
September 22, 2015: Oncotarget
Lionel Apetoh, Mark J Smyth, Charles G Drake, Jean-Pierre Abastado, Ron N Apte, Maha Ayyoub, Jean-Yves Blay, Marc Bonneville, Lisa H Butterfield, Anne Caignard, Chiara Castelli, Federica Cavallo, Esteban Celis, Lieping Chen, Mario P Colombo, Begoña Comin-Anduix, Georges Coukos, Madhav V Dhodapkar, Glenn Dranoff, Ian H Frazer, Wolf-Hervé Fridman, Dmitry I Gabrilovich, Eli Gilboa, Sacha Gnjatic, Dirk Jäger, Pawel Kalinski, Howard L Kaufman, Rolf Kiessling, John Kirkwood, Alexander Knuth, Roland Liblau, Michael T Lotze, Enrico Lugli, Francesco Marincola, Ignacio Melero, Cornelis J Melief, Thorsten R Mempel, Elizabeth A Mittendorf, Kunle Odun, Willem W Overwijk, Anna Karolina Palucka, Giorgio Parmiani, Antoni Ribas, Pedro Romero, Robert D Schreiber, Gerold Schuler, Pramod K Srivastava, Eric Tartour, Danila Valmori, Sjoerd H van der Burg, Pierre van der Bruggen, Benoît J van den Eynde, Ena Wang, Weiping Zou, Theresa L Whiteside, Daniel E Speiser, Drew M Pardoll, Nicholas P Restifo, Ana C Anderson
Whereas preclinical investigations and clinical studies have established that CD8(+) T cells can profoundly affect cancer progression, the underlying mechanisms are still elusive. Challenging the prevalent view that the beneficial effect of CD8(+) T cells in cancer is solely attributable to their cytotoxic activity, several reports have indicated that the ability of CD8(+) T cells to promote tumor regression is dependent on their cytokine secretion profile and their ability to self-renew. Evidence has also shown that the tumor microenvironment can disarm CD8(+) T cell immunity, leading to the emergence of dysfunctional CD8(+) T cells...
April 2015: Oncoimmunology
Liqun Luo, Gefeng Zhu, Haiying Xu, Sheng Yao, Gang Zhou, Yuwen Zhu, Koji Tamada, Lanqing Huang, Andrew D Flies, Megan Broadwater, William Ruff, Jan M A van Deursen, Ignacio Melero, Zhou Zhu, Lieping Chen
B7-H3 is a cell surface molecule in the immunoglobulin superfamily that is frequently upregulated in response to autoantigens and pathogens during host T cell immune responses. However, B7-H3's role in the differential regulation of T cell subsets remains largely unknown. Therefore, we constructed a new B7-H3 deficient mouse strain (B7-H3 KO) and evaluated the functions of B7-H3 in the regulation of Th1, Th2, and Th17 subsets in experimental autoimmune encephalomyelitis (EAE), experimental asthma, and collagen-induced arthritis (CIA); these mouse models were used to predict human immune responses in multiple sclerosis, asthma, and rheumatoid arthritis, respectively...
2015: PloS One
Bettina Weigelin, Elixabet Bolaños, Alvaro Teijeira, Ivan Martinez-Forero, Sara Labiano, Arantza Azpilikueta, Aizea Morales-Kastresana, José I Quetglas, Esther Wagena, Alfonso Rodríguez Sánchez-Paulete, Lieping Chen, Peter Friedl, Ignacio Melero
Cancer immunotherapy is undergoing significant progress due to recent clinical successes by refined adoptive T-cell transfer and immunostimulatory monoclonal Ab (mAbs). B16F10-derived OVA-expressing mouse melanomas resist curative immunotherapy with either adoptive transfer of activated anti-OVA OT1 CTLs or agonist anti-CD137 (4-1BB) mAb. However, when acting in synergistic combination, these treatments consistently achieve tumor eradication. Tumor-infiltrating lymphocytes that accomplish tumor rejection exhibit enhanced effector functions in both transferred OT-1 and endogenous cytotoxic T lymphocytes (CTLs)...
June 16, 2015: Proceedings of the National Academy of Sciences of the United States of America
Matthew Tontonoz, Connie E Gee
The 22nd annual Cancer Research Institute (CRI) International Immunotherapy Symposium was held from October 5-8, 2014, in New York City. Titled "Cancer Immunotherapy: Out of the Gate," the symposium began with a Cancer Immunotherapy Consortium satellite meeting focused on issues in immunotherapy drug development, followed by five speaker sessions and a poster session devoted to basic and clinical cancer immunology research. The second annual William B. Coley lecture was delivered by Lieping Chen, one of the four recipients of the 2014 William B...
May 2015: Cancer Immunology Research
Hyo Jin Park, Joon Seok Park, Yun Hee Jeong, Jimin Son, Young Ho Ban, Byoung-Hee Lee, Lieping Chen, Jun Chang, Doo Hyun Chung, Inhak Choi, Sang-Jun Ha
Regulatory T (Treg) cells act as terminators of T cell immuniy during acute phase of viral infection; however, their role and suppressive mechanism in chronic viral infection are not completely understood. In this study, we compared the phenotype and function of Treg cells during acute or chronic infection with lymphocytic choriomeningitis virus. Chronic infection, unlike acute infection, led to a large expansion of Treg cells and their upregulation of programmed death-1 (PD-1). Treg cells from chronically infected mice (chronic Treg cells) displayed greater suppressive capacity for inhibiting both CD8(+) and CD4(+) T cell proliferation and subsequent cytokine production than those from naive or acutely infected mice...
June 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Dallas B Flies, Tomoe Higuchi, Lieping Chen
PD-1H is a recently identified cell surface coinhibitory molecule of the B7/CD28 immune modulatory gene family. We showed previously that single injection of a PD-1H agonistic mAb protected mice from graft-versus-host disease (GVHD). In this study, we report two distinct mechanisms operate in PD-1H-induced T cell tolerance. First, signaling via PD-1H coinhibitory receptor potently arrests alloreactive donor T cells from activation and expansion in the initiation phase. Second, donor regulatory T cells are subsequently expanded to maintain long-term tolerance and GVHD suppression...
June 1, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Fan Zhou, Wei Wei, Chenhui Ling, Lieping Guo, Haotian Shi, Lu Li, Xiaoling Chen, Jian Hou
OBJECTIVE: To observe treatment response, survival, safety and the improvement of ECOG in patients with refractory multiple myeloma (MM) with serious heart failure after the administration of continuous low-dose of cyclophosphamide combined with prednisone (CP). METHODS: From January 2005 to September 2013, a total of 75 patients were treated by metronomic chemotherapy with continuous low-dose cyclophosphamide (50 mg/d) and prednisone (15 mg/d). RESULTS: Among the 75 patients, 2 were lost for follow-up...
March 2015: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Harriet M Kluger, Christopher R Zito, Meaghan L Barr, Marina K Baine, Veronica L S Chiang, Mario Sznol, David L Rimm, Lieping Chen, Lucia B Jilaveanu
PURPOSE: Programmed death ligand-1 (PD-L1) tumor expression represents a mechanism of immune escape for melanoma cells. Drugs blocking PD-L1 or its receptor have shown unprecedented activity in melanoma, and our purpose was to characterize tumor PD-L1 expression and associated T-cell infiltration in metastatic melanomas. EXPERIMENTAL DESIGN: We used a tissue microarray (TMA) consisting of two cores from 95 metastatic melanomas characterized for clinical stage, outcome, and anatomic site of disease...
July 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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