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BLOOD 2008年第8期111卷 3911-3912页

作者： McVicar, Daniel W. National Cancer Institute Cancer And Inflammation Program USA.

In this issue of Blood, Kondadasula and colleagues provide important clues for understanding successful cancer immunotherapy by demonstrating an intriguing mechanism through which CD16 synergizes with IL-12 to induce ... 详细信息

关键词： .IL receptor NK cells ITAMs

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Anti-PD1 in the wonder-gut-land

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细胞研究（英文版） 2018年第3期28卷 263-264页

作者： Marie Vetizou Giorgio Trinchieri Cancer and Inflammation Program Center for Cancer Research National Cancer InstituteNational Institutes of Health Bethesda MD 20892 USA

After the initial success of cancer immunotherapy using immune checkpoint blockers,the challenge is to understand why only a minority of patients respond to the therapy and to increase the rate of *** recent papers now report that the gut microbiota modulates the response to anti-PD1 therapy in patients with epithelial cancers or melanoma.

关键词： @@

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Improvements in the Prevention and Treatment of Anthrax Infection

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Procedia in Vaccinology 2009年第1期1卷 89-96页

作者： Klinman, Dennis M. Tross, Debra Cancer and Inflammation Program National Cancer Institute Frederick MD 21702 United States

Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs mimic the immunostimulatory activity of bacterial DNA. CpG ODN are finding use as vaccine adjuvants based on their ability to increase the speed, magnitude and duration of vaccine-specific immune responses. We conducted studies examining the capacity of CpG ODN to accelerate and prolong the protection induced by AVA (Anthrax Vaccine Adsorbed). Co-administering CpG-adjuvanted AVA with Dalbavancin, a long-activity antibiotic, protected naive mice from both the immediate and long-term threat posed by exposure to anthrax spores. A majority of animals immunized only once with CpG-adjuvanted AVA maintained resistance to anthrax infection for more than one year, even after their Ab titers declined to sub-protective levels. This survival was mediated by the de novo production of protective Abs by high affinity long-lived memory B cells that were generated by vaccination with CpG-adjuvanted AVA. © 2009.

关键词： Adjuvant Anthrax Vaccine

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Genetics and genomics of prostate cancer

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Asian Journal of Andrology 2013年第3期15卷 309-313页

作者： Michael Dean Hong LOU Cancer and Inflammation Program National Cancer Institute National Institutes of Health Frederick MD 21702 USA Basic Science Program SAIC-Frederick Nationa Cancer Institute National Institutes of Health Frederick MD 21702 USA

Prostate cancer （PCa） is one of the most common malignancies in the world with over 890 000 cases and over 258 000 deaths worldwide each year. Nearly all mortalities from PCa are due to metastatic disease, typically through tumors that evolve to be hormone-refractory or castrate-resistant. Despite intensive epidemiological study, there are few known environmental risk factors, and age and family history are the major determinants. However, there is extreme heterogeneity in PCa incidence worldwide, suggesting that major determining factors have not been described. Genome-wide association studies have been performed and a considerable number of significant, but low-risk loci have been identified. In addition, several groups have analyzed PCa by determination of genomic copy number, fusion gene generation and targeted resequencing of candidate genes, as well as exome and whole genome sequencing. These initial studies have examined both primary and metastatic tumors as well as murine xenografts and identified somatic alterations in TP53and other potential driver genes, and the disturbance of androgen response and cell cycle pathways. It is hoped that continued characterization of risk factors as well as gene mutation and misregulation in tumors will aid in understanding, diagnosing and better treating PCa.

关键词： androgen receptor cancer progression chromatin remodeling metastasis prostate cancer （PCa） risk factor somaticmutation tumor heterogeneity

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Quantitative Analysis of Colonic Epithelial Cell Aging in a Cell-cycle like Model: Changes in Nucleus and Cytoplasm Along the Crypt Axis

Quantitative Analysis of Colonic Epithelial Cell Aging in a ...

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Medical Imaging 2025: Digital and Computational Pathology

作者： Bao, Shunxing Wang, Yaohong Rudravaram, Gaurav Zhang, Rendong Deng, Ruining Yu, Xin Gao, Chenyu Li, Jia Li, Yike Roland, Joseph T. Zuo, Lianrui Liu, Qi Lau, Ken S. Coburn, Lori A. Wilson, Keith T. Landman, Bennett A. Huo, Yuankai Department of Electrical and Computer Engineering Vanderbilt University NashvilleTN United States Department of Anatomical Pathology UT MD Anderson Cancer Center HoustonTX United States Department of Computer Science Vanderbilt University NashvilleTN United States Department of Biostatistics Vanderbilt University Medical Center Nashville United States Department of Otolaryngology-Head and Neck Surgery Vanderbilt University Medical Center NashvilleTN United States Department of Surgery Vanderbilt University Medical Center NashvilleTN United States Department of Cell and Developmental Biology Vanderbilt University School of Medicine NashvilleTN United States Vanderbilt University Medical Center Division of Gastroenterology Hepatology and Nutrition Department of Medicine Nashville United States Vanderbilt University Medical Center Vanderbilt Center for Mucosal Inflammation and Cancer Nashville United States Vanderbilt University School of Medicine Program in Cancer Biology Nashville United States Veterans Affairs Tennessee Valley Healthcare System NashvilleTN United States Vanderbilt University Medical Center Department of Pathology Microbiology and Immunology NashvilleTN United States

ISBN: (纸本)9781510686045

Understanding epithelial cell aging in bowel tissue can provide critical insights into gastrointestinal (GI) health, potentially leading to improved diagnosis, treatment, and prevention strategies for various GI conditions. Despite the significance of cellular aging in the GI tract, previous studies have not quantified epithelial cell maturity development along the base-to-surface axis of colon crypts due to the labor-intensive nature of manual quantification and the lack of a clear definition of cellular age. Moreover, the process faces tremendous challenges when tissue is cut in 2D and examines results solely from one or a few biopsy cuts without reconstructing the full 3D space, as the original cell structure is 3D, leading to variability based on the cut angle. This research addresses these challenges by systematically analyzing the relationship between epithelial cell morphology and their position from the base to the surface in colon crypt tissue. Our approach involves using multiplex immunofluorescence (MxIF) imaging for cell nuclei segmentation, identifying the potential full longitudinal cut, and manually annotating the surface and base of the colon crypts. By analyzing the epithelial cells, we create density maps to investigate the relationship between nucleus size and the surface-to-base distance ratio, defining this ratio as cell age. We also examine the nucleus-to-cytoplasm (N/C) ratio in relation to cell age. For the statistical analysis, we use a robust linear regression model to remove outliers and a random effects model for the final regression. Our results show a decreasing trend in both the N/C ratio and nucleus size as epithelial cells move from the base to the surface. These findings provide a quantitative pipeline for single-cell profiling in a spatial manner, facilitating broader analysis of epithelial cell aging and its implications for GI health. © 2025 SPIE.

关键词： Linear regression

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Chemokines: the past, the present and the future

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Cellular & Molecular Immunology 2018年第4期15卷 295-298页

作者： Peng Tang Ji Ming Wang Department of Breast Surgery Southwest HospitalArmy Medical UniversityChongqing 400038China Cancer and Inflammation Program Center for Cancer ResearchNational Cancer Institute at FrederickFrederick 21702MDUSA

We are very excited to publish our article in the“Chemokine Special Issue”of Cellular and Molecular Immunology,which has received increasing attention in the field of immunology.A natural question emerging regarding this issue is,why chemokines?The answer may of course not be simple,but if we consider only the essential,a shortened answer should be because chemokines are among the first mobilizers of host responses in homeostasis and diseases associated with inflammation(Figure 1).

关键词： has Figure among

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Identifying Cellular Neighborhood Phenotypes Differentiating Normal and Quiescent Crohn's Disease via MxIF

Identifying Cellular Neighborhood Phenotypes Differentiating...

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Medical Imaging 2025: Digital and Computational Pathology

作者： Rudravaram, Gaurav Bao, Shunxing Krishnan, Aravind R. Remedios, Lucas W. Kim, Michael E. Saunders, Adam M. Liu, Qi Lau, Ken S. Roland, Joseph T. Washington, Mary K. Coburn, Lori A. Wilson, Keith T. Huo, Yuankai Landman, Bennett A. Department of Electrical and Computer Engineering Vanderbilt University NashvilleTN United States Department of Computer Science Vanderbilt University NashvilleTN United States Division of Gastroenterology Hepatology and Nutrition Department of Medicine Vanderbilt University Medical Center NashvilleTN United States Vanderbilt Center for Mucosal Inflammation and Cancer Vanderbilt University Medical Center NashvilleTN United States Program in Cancer Biology Vanderbilt University School of Medicine NashvilleTN United States Veterans Affairs Tennessee Valley Healthcare System NashvilleTN United States Department of Pathology Microbiology and Immunology Vanderbilt University Medical Center NashvilleTN United States Center for Quantitative Sciences Vanderbilt University Medical Center NashvilleTN United States Epithelial Biology Center Vanderbilt University Medical Center NashvilleTN United States Department of Cell and Developmental Biology Vanderbilt University School of Medicine NashvilleTN United States Vanderbilt University Department of Biomedical Engineering Nashville United States Department of Biostatistics Vanderbilt University Medical Center Nashville United States

ISBN: (纸本)9781510686045

Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract characterized by alternating periods of activity and remission. This study investigates whether the cellular environments of quiescent (inactive disease) and normal tissues show similarities or differences, exploring potential residual effects from disease and tissue recovery patterns. While active CD can typically be characterized by high neutrophil density, whereas quiescent tissues present less pronounced inflammatory markers. This study leverages multiplexed immunofluorescence (MxIF) data to examine the distributions and patterns of various nuclei subtypes in quiescent versus normal tissues, aiming to determine how similar or different these tissues are in the absence of active inflammation. In our study, we analyze four tissue samples labeled as normal and five as quiescent from CD patients, as determined by a pathologist. We use rigid and deformable registration of MxIF images to analyze these tissues in a unified space and classify the nuclei into 13 subtypes. Using a KD tree, we identify the 10 nearest neighbors for each nucleus, building a combined distance-weighted neighborhood matrix representing both normal and quiescent tissues. We projected these neighborhoods into 2 dimensions using t-distributed stochastic nearest neighbor(t-SNE), clustered them, and calculated the enrichment for each subtype between normal and quiescent states within each of 20 and 40 clusters. In the 20-cluster analysis, we find monocytes enrich in one cluster and leukocytes enrich in two clusters for normal and quiescent tissues respectively. For the 40-cluster analysis, we observe monocytes, macrophages, and leukocytes enrich in one cluster each in normal tissues, and in the quiescent condition, one cluster enriched with enteroendocrine cells, and two clusters enriched with leukocytes. The results were statistically significant as determined by a chi-squared test (p © 2025 SPIE.

关键词： Tissues White blood cells Diseases and disorders Biological samples Matrices Statistical analysis Image segmentation Image registration Critical dimension metrology inflammation

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Single-cell RNA sequencing-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma

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Journal of Hepatology 2025年第6期82卷 1036-1049页

作者： Cappuyns, Sarah Piqué-Gili, Marta Esteban-Fabró, Roger Philips, Gino Balaseviciute, Ugne Pinyol, Roser Gris-Oliver, Albert Vandecaveye, Vincent Abril-Fornaguera, Jordi Montironi, Carla Bassaganyas, Laia Peix, Judit Zeitlhoefler, Marcus Mesropian, Agavni Huguet-Pradell, Júlia Haber, Philipp K. Figueiredo, Igor Ioannou, Giorgio Gonzalez-Kozlova, Edgar Mohr, Raphael Meyer, Tim Lachenmayer, Anja Marquardt, Jens U. Reeves, Helen L. Edeline, Julien Finkelmeier, Fabian Trojan, Jörg Galle, Peter R. Foerster, Friedrich Mínguez, Beatriz Montal, Robert Gnjatic, Sacha Pinato, David J. Heikenwalder, Mathias Verslype, Chris Van Cutsem, Eric Lambrechts, Diether Villanueva, Augusto Dekervel, Jeroen Llovet, Josep M. Digestive Oncology Department of Gastroenterology University Hospitals Leuven Leuven Belgium Laboratory of Clinical Digestive Oncology Department of Oncology KU Leuven Leuven Belgium Laboratory for Translational Genetics Department of Human Genetics KU Leuven Leuven Belgium VIB Centre for Cancer Biology Leuven Belgium Mount Sinai Liver Cancer Program (Divisions of Liver Diseases Department of Hematology/Oncology Department of Medicine) Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York United States Liver Cancer Translational Research Group Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Hospital Clínic Universitat de Barcelona Catalonia Barcelona Spain Radiology Department University Hospitals Leuven Leuven Belgium Laboratory of Translational MRI Department of Imaging and Pathology KU Leuven Leuven Belgium Pathology Department and Molecular Biology Core Hospital Clínic of Barcelona Barcelona Spain Institut de Génomique Fonctionnelle Univ. Montpellier CNRS INSERM Montpellier France Department of Surgery Campus Charité Mitte and Campus Virchow-Klinikum Charité-Universitätsmedizin Berlin Berlin 13353 Germany Department of Immunology and Immunotherapy Icahn School of Medicine at Mount Sinai New York NY United States Department of Surgery & Cancer Imperial College London Hammersmith Hospital London United Kingdom Department of Hepatology and Gastroenterology Charité - Universitätsmedizin Berlin Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM) Berlin Germany Research Department of Oncology UCL Cancer Institute University College London Royal Free Hospital London United Kingdom Department of Visceral Surgery and Medicine Inselspital Bern University Hospital University of Bern Bern Switzerland Department of Medicine I University Medical Center Schleswig Holstein Campus Lübeck Lübeck Germany Hepatopancreatobiliary Multidisciplinary Team Newcastle upon Tyne NHS Foundation Trust Freeman Hospital New

Background & Aims: The combination of atezolizumab and bevacizumab (atezo+bev) is the current standard of care for advanced hepatocellular carcinoma (HCC), providing a median overall survival (OS) of 19.2 months. Here, we aim to uncover the underlying cellular processes driving clinical benefit vs. resistance to atezo+bev. Methods: We harnessed the power of single-cell RNA sequencing in advanced HCC to derive gene expression signatures recapitulating 21 cell phenotypes. These signatures were applied to 422 RNA-sequencing samples of patients with advanced HCC treated with atezo+bev (n = 317) vs. atezolizumab (n = 47) or sorafenib (n = 58) as comparators. Results: We unveiled two distinct patterns of response to atezo+bev. First, an immune-mediated response characterised by the combined presence of CD8+ T effector cells and pro-inflammatory CXCL10+ macrophages, representing an immune-rich microenvironment. Second, a non-immune, angiogenesis-related response distinguishable by a reduced expression of the VEGF co-receptor neuropilin-1 (NRP1), a biomarker that specifically predicts improved OS upon atezo+bev vs. sorafenib (p = 0.039). Primary resistance was associated with an enrichment of immunosuppressive myeloid populations, namely CD14+ monocytes and TREM2+ macrophages, and Notch pathway activation. Based on these mechanistic insights we define “Immune-competent” and “Angiogenesis-driven” molecular subgroups, each associated with a significantly longer OS with atezo+bev vs. sorafenib (p of interaction = 0.027), and a “Resistant” subset. Conclusion: Our study unveils two distinct molecular subsets of clinical benefit to atezolizumab plus bevacizumab in advanced HCC (“Immune-competent” and “Angiogenesis-driven”) as well as the main traits of primary resistance to this therapy, thus providing a molecular framework to stratify patients based on clinical outcome and guiding potential strategies to overcome resistance. Impact and implications: Atezolizumab + bevacizumab (a

关键词： Advanced Hepatocellular Carcinoma Atezolizumab and bevacizumab Biomarkers of Response Primary Resistance Single-Cell RNA-Sequencing

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Human monoclonal antibodies as candidate therapeutics against emerging viruses

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Frontiers of Medicine 2017年第4期11卷 462-470页

作者： Yujia Jin Cheng Lei Dan Hu Dimiter S. Dimitrov Tianlei Ying Key Laboratory of Medical Molecular Virology of the Ministries of Education and Health School of Basic Medical Sciences Fudan University Shanghai 200032 China Protein Interactions Section Cancer and Inflammation Program Center for Cancer Research National Cancer Institute National Institutes of Health Frederick MD 21702 USA

The emergence of new pathogens, such as severe acute respiratory syndrome coronavirus （SARS-CoV）, Middle East respiratory syndrome coronavirus （MERS-CoV）, and Ebola virus, poses serious challenges to global public health and highlights the urgent need for novel antiviral approaches. Monoclonal antibodies （mAbs） have been successfully used to treat various diseases, particularly cancer and immunological disorders. Antigen-specific mAbs have been isolated using several different approaches, including hybridoma, transgenic mice, phage display, yeast display, and single B-celi isolation. Consequently, an increasing number of mAbs, which exhibit high potency against emerging viruses in vitro and in animal models of infection, have been developed. In this paper, we summarize historical trends and recent developments in mAb discovery, compare the advantages and disadvantages of various approaches to mAb production, and discuss the potential use of such strategies for the development of antivirals against emerging diseases. We also review the application of recently developed human mAbs against SARS-CoV, MERS-CoV, and Ebola virus and discuss prospects for the development of mAbs as therapeutic agents against emerging viral diseases.

关键词： human monoclonal antibodies emerging infectious diseases SARS-CoV MERS-CoV Ebola virus

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Lupus nephritis: Animal modeling of a complex disease syndrome pathology

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Drug Discovery Today: Disease Models 2014年 11卷 13-18页

作者： McGaha, Tracy L. Madaio, Michael P. Cancer Immunology Inflammation and Tolerance Program GRU Cancer Center Georgia Regents University United States Department of Medicine Medical College of Georgia Georgia Regents University United States

Nephritis as a result of autoimmunity is a common morbidity associated with Systemic Lupus Erythematosus (SLE). There is substantial clinical and industry interest in medicinal intervention in the SLE nephritic process;however, clinical trials to specifically treat lupus nephritis have not resulted in complete and sustained remission in all patients. Multiple mouse models have been used to investigate the pathologic interactions between autoimmune reactivity and SLE pathology. While several models bear a remarkable similarity to SLE-driven nephritis, there are limitations for each that can make the task of choosing the appropriate model for a particular aspect of SLE pathology challenging. This is not surprising given the variable and diverse nature of human disease. In many respects, features among murine strains mimic some (but never all) of the autoimmune and pathologic features of lupus patients. Although the diversity often limits universal conclusions relevant to pathogenesis, they provide insights into the complex process that result in phenotypic manifestations of nephritis. Thus nephritis represents a microcosm of systemic disease, with variable lesions and clinical features. In this review, we discuss some of the most commonly used models of lupus nephritis (LN) and immune-mediated glomerular damage examining their relative strengths and weaknesses, which may provide insight in the human condition. © 2014 Elsevier Ltd.

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