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Lieping Chen

Ling Chen, Takeshi Azuma, Weiwei Yu, Xu Zheng, Liqun Luo, Lieping Chen
Induced B7-H1 expression in the tumor microenvironment initiates adaptive resistance, which impairs immune functions and leads to tumor escape from immune destruction. Antibody blockade of the B7-H1/PD-1 interaction overcomes adaptive resistance, leading to regression of advanced human cancers and survival benefits in a significant fraction of patients. In addition to cancer cells, B7-H1 is expressed on dendritic cells (DCs), but its role in DC functions is less understood. DCs can present multiple antigens (Ags) to stimulate dominant or subdominant T cell responses...
March 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ning Lu, Ying Li, Zhiqiang Zhang, Junji Xing, Ying Sun, Sheng Yao, Lieping Chen
Semaphorin-4A (Sema4A) has been implicated in the co-stimulation of T cells and drives Th1 immune responses by binding to the receptor T-cell immunoglobulin and mucin domain protein 2 (Tim-2) in mice. Here we show that human, but not murine, Sema4A is preferentially expressed on antigen-presenting cells, and co-stimulates CD4+ T-cell proliferation and drives Th2 responses. By employing two independent cloning strategies, we demonstrate that Immunoglobulin-like transcript 4 (ILT-4) is a receptor for human SEMA4A (hSEMA4A) on activated CD4+ T cells...
February 21, 2018: Nature Communications
Qian Xiao, Jibo Wu, Wei-Jia Wang, Shiyang Chen, Yingxia Zheng, Xiaoqing Yu, Katrina Meeth, Mahnaz Sahraei, Alfred L M Bothwell, Lieping Chen, Marcus Bosenberg, Jianfeng Chen, Veronika Sexl, Le Sun, Lin Li, Wenwen Tang, Dianqing Wu
Immunotherapy offers new options for cancer treatment, but efficacy varies across cancer types. Colorectal cancers (CRCs) are largely refractory to immune-checkpoint blockade, which suggests the presence of yet uncharacterized immune-suppressive mechanisms. Here we report that the loss of adenomatosis polyposis coli (APC) in intestinal tumor cells or of the tumor suppressor PTEN in melanoma cells upregulates the expression of Dickkopf-related protein 2 (DKK2), which, together with its receptor LRP5, provides an unconventional mechanism for tumor immune evasion...
March 2018: Nature Medicine
Franz Villarroel-Espindola, Xiaoqing Yu, Ila Datar, Nikita Mani, Miguel Sanmamed, Vamsidhar Velcheti, Konstantinos Syrigos, Maria Toki, Hongyu Zhao, Lieping Chen, Roy S Herbst, Kurt A Schalper
Purpose: Determine the localized expression pattern and clinical significance of VISTA/PD-1H in human non-small cell lung cancer (NSCLC). Experimental Design: Using multiplex quantitative immunofluorescence (QIF), we performed localized measurements of VISTA, PD-1, and PD-L1 protein in 758 stage I-IV NSCLCs from 3 independent cohorts represented in tissue microarray format. The targets were selectively measured in cytokeratin+ tumor epithelial cells, CD3+ T cells, CD4+ T-helper cells, CD8+ cytotoxic T cells, CD20+ B lymphocytes and CD68+ tumor-associated macrophages...
December 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Malgorzata Drabczyk-Pluta, Tanja Werner, Daniel Hoffmann, Qibin Leng, Lieping Chen, Ulf Dittmer, Gennadiy Zelinskyy
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) can suppress T cell responses in several different diseases. Previously these suppressive cells were observed to expand in HIV patients and in a mouse retrovirus model, yet their suppressive effect on virus-specific CD8(+) T cells in vitro and in vivo has not been characterized thus far. RESULTS: We used the Friend retrovirus (FV) model to demonstrate that MDSCs expand and become activated during the late phase of acute FV infection...
August 23, 2017: Retrovirology
Qi Wang, Jianwei He, Dallas B Flies, Liqun Luo, Lieping Chen
Programmed death one homolog (PD-1H) is an immunoglobulin superfamily molecule and primarily acts as a coinhibitor in the initiation of T cell response to antigens. Here, we report that genetic ablation of PD-1H in mice blocks the differentiation of naive T cells to Foxp3(+) inducible Treg cells (iTreg) with a significant decrease of iTreg in lymphoid organs. This effect of PD-1H is highly specific for iTreg because both naturally generated iTreg in gut-related tissues and in vitro induced iTreg by TGF-β were decreased whereas the genesis of natural Treg (nTreg) remains normal...
July 20, 2017: Scientific Reports
Xinxin Nie, Wenni Chen, Ying Zhu, Baozhu Huang, Weiwei Yu, Zhanshuai Wu, Sizheng Guo, Yiping Zhu, Liqun Luo, Shengdian Wang, Lieping Chen
The role of B7-DC in T-cell responses remains controversial because both coinhibitory and costimulatory functions have been reported in various experimental systems in vitro and in vivo. In addition to interacting with the coinhibitory receptor PD-1, B7-DC has also been shown to bind repulsive guidance molecule b (RGMb). The functional consequences of the B7-DC/RGMb interaction, however, remain unclear. More than a decade ago, we reported that replacement of a murine B7-DC mutant lysine with serine (K113S) at positive 113 resulted in a loss of binding capacity to PD-1...
May 8, 2017: Cellular & Molecular Immunology
Huafeng Liu, Xin Li, Li Hu, Min Zhu, Bailin He, Liqun Luo, Lieping Chen
Programmed death one homolog (PD-1H) is a cell surface molecule of the B7/CD28 immune modulatory gene family. Although PD-1H has been shown to function as a coinhibitory receptor on T cells to limit naive T-cell activation and proliferation, its role in the regulation of the T-cell response to allergens is unknown. We report here that genetic ablation or blockade of PD-1H drastically promotes pulmonary inflammation with massive accumulation of eosinophils in a mouse model of experimental asthma, indicating a suppressive function of PD-1H in allergic inflammation...
May 8, 2017: Cellular & Molecular Immunology
Qitian Mu, Lieping Guo, Yongxian Hu, Lixia Sheng, Yi Zhang, Ningning Wu, Ying Chen, Cong Shi, Songqiu Shi, Ying Wu, Guifang Ouyang
No abstract text is available yet for this article.
September 2017: Leukemia & Lymphoma
Harriet M Kluger, Christopher R Zito, Gabriela Turcu, Marina K Baine, Hongyi Zhang, Adebowale Adeniran, Mario Sznol, David L Rimm, Yuval Kluger, Lieping Chen, Justine V Cohen, Lucia B Jilaveanu
Purpose: With recent approval of inhibitors of PD-1 in melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma, extensive efforts are under way to develop biomarkers predictive of response. PD-L1 expression has been most widely studied, and is more predictive in NSCLC than renal cell carcinoma or melanoma. We therefore studied differences in expression patterns across tumor types.Experimental Design: We used tissue microarrays with tumors from NSCLC, renal cell carcinoma, or melanoma and a panel of cell lines to study differences between tumor types...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Lijun Lei, Siyu Xia, Dan Liu, Xiaoqing Li, Jing Feng, Yaqi Zhu, Jun Hu, Linjian Xia, Lieping Guo, Fei Chen, Hui Cheng, Ke Chen, Hanyang Hu, Xiaohua Chen, Feng Li, Shan Zhong, Nupur Mittal, Guohua Yang, Zhijian Qian, Leng Han, Chunjiang He
No abstract text is available yet for this article.
February 15, 2017: Briefings in Bioinformatics
Jun Wang, Ruirong Yuan, Wenru Song, Jingwei Sun, Delong Liu, Zihai Li
The current success of targeted inhibition against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death 1/Programmed Death Ligand 1 (PD-1/PD-L1, herein collectively referred to as PD) pathways is hailed as a cancer immunotherapy breakthrough. PD-L1, known also as B7 homolog 1 (B7-H1), was initially discovered by Dr. Lieping Chen in 1999. To recognize the seminal contributions by Chen to the development of PD-directed therapy against cancer, the Chinese American Hematologist and Oncologist Network (CAHON) decided to honor him with its inaugural Lifetime Achievement Award in Hematology and Oncology at the CAHON's 2015 annual meeting...
January 25, 2017: Journal of Hematology & Oncology
Yu Zhang, Lieping Chen
No abstract text is available yet for this article.
November 1, 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 two independent populations. Associations between the marker levels, TILs, and major clinicopathologic variables were determined...
January 15, 2017: 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
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