A5085595853- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Complement system in diseases
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- CAR-T cell therapy research
- Blood groups and transfusion
- Cancer, Hypoxia, and Metabolism
- Eicosanoids and Hypertension Pharmacology
- Erythrocyte Function and Pathophysiology
- Cell Adhesion Molecules Research
- Cancer Cells and Metastasis
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Peptidase Inhibition and Analysis
- Heme Oxygenase-1 and Carbon Monoxide
- Pancreatic and Hepatic Oncology Research
- Glycosylation and Glycoproteins Research
- Renal Diseases and Glomerulopathies
- Immune Response and Inflammation
- Cancer Mechanisms and Therapy
- Viral-associated cancers and disorders
- Immunodeficiency and Autoimmune Disorders
- Mycobacterium research and diagnosis
Cold Spring Harbor Laboratory
2016-2025
Cornell University
2015-2025
Weill Cornell Medicine
2016-2024
University of Cambridge
2010-2020
Cancer Research UK
2005-2020
Cancer Research UK Cambridge Center
2012-2020
Athens University of Economics and Business
2020
Monash Medical Centre
2017
Wellcome Trust
2002-2013
Medical Research Council
2000-2013
Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether CAFs uniformly carry out these tasks or if subtypes of with distinct phenotypes PDA exist. We identified a CAF subpopulation elevated expression α-smooth muscle actin (αSMA) located immediately adjacent to neoplastic mouse human...
Significance Cancer immune evasion is well described. In some cases, this may be overcome by enhancing T-cell responses. We show that despite the presence of antitumor T cells, immunotherapeutic antibodies are ineffective in a murine pancreatic cancer model recapitulating human disease. Removing carcinoma-associated fibroblast (CAF) expressing activation protein (FAP) from tumors permitted control tumor growth and uncovered efficacy these antibodies. FAP + CAFs only tumoral source chemokine...
An optimal immune response should differentiate between harmful and innocuous antigens. Primitive systems of innate immunity, such as the complement system, may play a role in this distinction. When activated, C3 component attaches to potential antigens on microorganisms. To determine whether alters acquired recognition, mice were immunized with recombinant model antigen, hen egg lysozyme (HEL), fused murine C3d. HEL bearing two three copies C3d was 1000- 10,000-fold more immunogenic,...
Waking up in a trap Cancer patients who have undergone successful treatment can experience relapse of their disease years or even decades later. This is because cancer cells that disseminated beyond the primary tumor site enter state dormancy, where they remain viable but not proliferating. Eventually, by mechanisms are poorly understood, these clinically undetectable “wake up” and form actively growing metastases. Studying mouse models, Albrengues et al. found sustained lung inflammation...
The stromal microenvironment of tumors, which is a mixture hematopoietic and mesenchymal cells, suppresses immune control tumor growth. A cell type that was first identified in human cancers expresses fibroblast activation protein-α (FAP). We created transgenic mouse FAP-expressing cells can be ablated. Depletion made up only 2% all established Lewis lung carcinomas, caused rapid hypoxic necrosis both cancer immunogenic tumors by process involving interferon-γ factor-α. Depleting...
The complement system is an important mediator of the acute inflammatory response, and effective inhibitor would suppress tissue damage in many autoimmune diseases. Such might be found among endogenous regulatory proteins that block enzymes activate C3 C5. Of these proteins, receptor type 1 (CR1; CD35) has most inhibitory potential, but its restriction to a few cell types limits function vivo. This limitation was overcome by recombinant, soluble human CR1, sCR1, which lacks transmembrane...
Identity of the Epstein-Barr virus (EBV) receptor with complement type 2 (CR2) was established in three sets experiments using monoclonal antibodies, HB-5 and anti-B2, which recognize a Mr 145,000 B-lymphocyte membrane protein that is CR2. First, rank order for binding fluoresceinated EBV to four lymphoblastoid cell lines (SB, JY, Raji, Molt-4) identical anti-B2 by analytical flow cytometry. Second, pretreatment cells followed treatment goat F(ab')2 fragments mouse IgG blocked on SB,...
Lymphocytes must proliferate and differentiate in response to low concentrations of a vast array antigens. The requirements broad specificity sensitivity conflict because the former is met by low-affinity antigen receptors, which precludes achieving latter with high-affinity receptors. Coligation membrane protein CD19 receptor B lymphocytes decreased threshold for receptor-dependent stimulation two orders magnitude. proliferated when approximately 100 receptors per cell, 0.03 percent total,...
CD22 is a membrane immunoglobulin (mIg)-associated protein of B cells. tyrosine-phosphorylated when mIg ligated. Tyrosine-phosphorylated binds and activates SHP, tyrosine phosphatase known to negatively regulate signaling through mIg. Ligation prevent its coaggregation with lowers the threshold at which cell by factor 100. In secondary lymphoid organs, may be sequestered away from interactions counterreceptors on T Thus, molecular switch for SHP that bias anatomic sites rich in
A function of P in the alternative complement pathway is to prolong first order decay hemolytic sites on EAC43B a dose-dependent manner. As number initial convertase not changed, even when activated properdin (P) increases t1/2 10-fold or more, acts stabilize rather than uncover additional sites. binds EAC43 generate EAC43P reaction that proceeds slightly more rapidly at 15 degrees C 0 C, but reaches same plateau and does require divalent cations. The presence only stabilizes subsequently...
An activity that is inhibitory to the properdin-stabilized amplification C3 convertase (C3b,Bb,P) was solubilized from human erythrocyte (E hu ) membranes by Nonidet P-40 and purified homogeneity. The membrane glycoprotein had an apparent M r of 1-1.2×10 6 on gel filtration in presence P-40. On sodium dodecyl sulfate/polyacrylamide electrophoresis it presented a single stained band with 205,000, or without prior reduction disulfides. protein E produced dose-related, first-order decay...
Sheep erythrocytes in their native state did not activate the alternative complement pathway, as measured by lysis dilutions of normal human serum containing [ethylenebis(oxyethylenenitrilo)] tetraacetic acid but acquired this capacity after membrane sialic residues had been removed (by sialidase) or modified NaIO 4 ). Activation pathway sheep required removal modification at least 40% to reach threshold, and it increased proportionately when larger amounts affected. Studies with isolated...
Spermatogonial stem cells (SSCs) are the foundation for spermatogenesis and, thus, preservation of a species. Because cell rarity, studying their self-renewal is greatly facilitated by in vitro culture enriched biologically active populations. A recently developed method identified glial line-derived neurotrophic factor (GDNF) as essential growth that supports SSCs and results an increase number. This system good model to study mechanisms because well defined conditions, population,...
Fibroblast activation protein-α (FAP) identifies stromal cells of mesenchymal origin in human cancers and chronic inflammatory lesions. In mouse models cancer, they have been shown to be immune suppressive, but studies their occurrence function normal tissues limited. With a transgenic line permitting the bioluminescent imaging FAP+ cells, we find that reside most adult mouse. from three sites, skeletal muscle, adipose tissue, pancreas, highly similar transcriptomes, suggesting shared...
The erythrocytes of patients with systemic lupus erythematosus have been shown to a decreased number receptors for the major cleavage fragment third component complement (C3b). We studied basis this C3b by measuring uptake anti-C3b-receptor antibody on cells from 113 normal subjects, 38 erythematosus, 14 their spouses, and 47 relatives. subjects had 5014 +/- (mean S.E.M.) receptor sites per cell, but relatives significantly fewer sites--2809 241 3167 196, respectively (P less than 0.0005)....