A5056729409- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Lung Cancer Treatments and Mutations
- RNA modifications and cancer
- Sphingolipid Metabolism and Signaling
- Cancer Genomics and Diagnostics
- vaccines and immunoinformatics approaches
- Cell Adhesion Molecules Research
- Lipid metabolism and biosynthesis
- Immune cells in cancer
- SARS-CoV-2 and COVID-19 Research
- Cancer Cells and Metastasis
- Melanoma and MAPK Pathways
- Ferroptosis and cancer prognosis
- Peptidase Inhibition and Analysis
- CAR-T cell therapy research
- Lymphoma Diagnosis and Treatment
- RNA Interference and Gene Delivery
- Endoplasmic Reticulum Stress and Disease
- Lung Cancer Diagnosis and Treatment
- Platelet Disorders and Treatments
- Radiopharmaceutical Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- PARP inhibition in cancer therapy
- Lipid metabolism and disorders
University of Oslo
2023-2024
Oslo University Hospital
2023-2024
The University of Texas MD Anderson Cancer Center
2015-2024
University of Kentucky
2006-2018
Mario Negri Sud Foundation
2004-2014
Lexington VA Health Care System
2014
Hypertension Institute
2014
Center for Systems Biology
2009-2010
Genomic intratumor heterogeneity (ITH) may be associated with postsurgical relapse of localized lung adenocarcinomas. Recently, mutations, through generation neoantigens, were shown to alter tumor immunogenicity T-cell responses. Here, we performed sequencing the receptor (TCR) in 45 regions from 11 adenocarcinomas and observed substantial differences density clonality majority clones restricted individual regions. TCR ITH positively correlated predicted neoantigen ITH, suggesting that...
Abstract PARP inhibitors have been proven clinically efficacious in platinum-responsive ovarian cancer regardless of BRCA1/2 status and breast cancers with germline mutation. However, resistance to may preexist or evolve during treatment many types be overcome by combining other therapies, such as immune checkpoint inhibitors, which confer durable responses are rapidly becoming the standard care for multiple tumor types. This study investigated therapeutic potential niraparib, a highly...
The lipid mediator lysophosphatidic acid (LPA) is a potent regulator of vascular cell function in vitro, but its physiologic role the cardiovasculature largely unexplored. To address LPA regulating platelet and thrombosis, we investigated effects on isolated murine platelets. Although activates platelets from majority human donors, found that treatment with concentrations attenuated agonist-induced aggregation. Transgenic overexpression autotaxin/lysophospholipase D (Enpp2), enzyme necessary...
8504 Background: Neoadjuvant immune checkpoint inhibitors (ICIs) induce major pathologic response (MPR) rates of 20 to 45% in resected NSCLCs. We report the results NEOSTAR - a phase 2 trial neoadjuvant N or NI for Methods: Pts with stage I-IIIA (single N2) resectable NSCLC (AJCC 7 th ), PS 0-1, were randomized (3 mg/kg IV, D1, 15, 29) plus I (1 D1) followed by surgery (n = 44). Primary endpoint: MPR (≤10% viable tumor), hypothesized be higher than induction chemotherapy historical controls....
To realize the full potential of immunotherapy, it is critical to understand drivers tumor infiltration by immune cells. Previous studies have linked with neoantigen levels, but broad applicability this concept remains unknown. Here, we find that while observation true across cancers characterized recurrent mutations, does not hold for driven copy number alterations, such as breast and pancreatic tumors. invasion in these cancers, developed an integrative multi-omics framework, identifying...
IntroductionThe combination of programmed cell death protein-1 or death-ligand 1 immune checkpoint blockade and chemotherapy has revolutionized the treatment advanced NSCLC, but mechanisms underlying this synergy remain incompletely understood. In study, we explored relationships between neoadjuvant microenvironment (IME) resectable NSCLC to identify novel by which may enhance effect blockade.MethodsGenomic, transcriptomic, profiling data 511 patients treated with followed surgery (NCT)...
Lipins are phosphatidic acid phosphatases with a pivotal role in regulation of triglyceride and glycerophospholipid metabolism. Lipin1 is also an amplifier PGC-1α, nuclear coactivator PPAR-α responsive gene transcription. do not contain recognized membrane-association domains, but interaction these enzymes cellular membranes necessary for access to their phospholipid substrate. We identified conserved polybasic amino motif N-terminal domain previously implicated as determinant localization...
Brown adipose tissue is a thermogenic organ that dissipates stored energy as heat to maintain body temperature. This process may also provide protection from development of diet-induced obesity. We report the bioactive lipid mediator lysophosphatidic acid (LPA) markedly decreases differentiation cultured primary brown adipocyte precursors, whereas potent selective inhibitors LPA-generating enzyme autotaxin (ATX) promote differentiation. Transgenic mice overexpressing ATX exhibit reduced...
Background The biological underpinnings of the prognostic and predictive significance a relative neutrophilia in patients with non-small lung cancer (NSCLC) are undefined. We sought to comprehensively examine relationships between circulating intratumoral neutrophil populations features immune contexture undergoing NSCLC resection. Methods Preoperative soluble cytokine angiogenic factors; tumor multiplex immunofluorescence; RNA, whole exome, T-cell receptor sequencing; flow cytometry were...
// Shreya Mitra 1 , Lorenzo Federico Wei Zhao Jennifer Dennison Tapasree Roy Sarkar 2 Fan Zhang Vinita Takiar 3 Kwai W. Cheng 4 Sendurai Mani 5 Ju Seog Lee Gordon B. Mills Department of Systems Biology, The University Texas MD Anderson Cancer Center, Houston, TX, USA Center for Statistical Bioinformatics, A&M University, College Station, Radiation Oncology, Cincinnati, OH, Cardiac Catheterization Laboratory, Michael and DeBakey Medical Translational Molecular Pathology, Correspondence to:...
Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) yielded clinical benefit in patients with checkpoint blockade immunotherapy-refractory non-small lung cancer (NSCLC) prompting a renewed interest TIL-ACT. This preclinical study explores the feasibility producing NSCLC TIL product sufficient numbers and enhanced attributes using an improved culture method.TIL from resected tumors were initially cultured (1) traditional method interleukin (IL)-2 alone 24-well plates (TIL...
In cell suspensions subjected to high-shear rotatory motion, human PMN (polymorphonuclear cells) adhered E-selectin-expressing CHO (Chinese-hamster ovary) cells (CHO-E), and formed homotypic aggregates when challenged by E-selectin–IgG fusion protein, a mechanism that involved β2 integrins. Both heterotypic adhesion was accompanied tyrosine phosphorylation of 110 kDa protein (P110). This event prevented blocking anti-(β2 integrin) antibodies inhibitors Src-family kinases, suggesting it part...
We previously reported that vascular endothelial growth factor (VEGF)-dependent activation of phospholipase Cgamma1 (PLCgamma) regulated tube stability by competing with phosphoinositide 3-kinase (PI3K) for their common substrate. Here we describe an additional mechanism which PLCgamma promoted regression tubes and blood vessels. Namely, it increased the level autotaxin (ATX), is a secreted form lysophospholipase D produces lysophosphatidic acid (LPA). LPA motility cells, leading to...
In human PMN (polymorphonuclear cells), challenged by P-selectin, the β2-integrin Mac-1 (macrophage antigen-1) promoted activation of SRC (cellular homologue Rous sarcoma virus oncogenic protein) family members HCK (haematopoietic cell kinase) and LYN (an protein tyrosine phosphorylation a P-110 (110 kDa protein). kinase activity in turn was necessary for macrophage antigen-1-mediated adhesion [Piccardoni, Sideri, Manarini, Piccoli, Martelli, de Gaetano, Cerletti Evangelista (2001) Blood 98,...
Platelet-neutrophil interactions play a key role in cardiovascular disease and inflammatory processes. Src family kinases mediate P-selectin glycoprotein ligand-1-Mac-1 cross talk necessary for firm platelet-neutrophil adhesion. Because kinase activity can be regulated by cAMP-dependent pathways, this work, we evaluated the of phosphodiesterases signaling events that are required to sustain neutrophil recruitment at site vascular injury.In neutrophils exposed P-selectin, selective...
Immunotherapies targeting immune checkpoints have proven efficacious in reducing the burden of lung cancer patients; however, antigenic targets these reinvigorated T cells remain poorly defined. Lung tumors contain tumor-associated macrophages (TAM) and neutrophils, which release serine proteases neutrophil elastase (NE) proteinase 3 (P3) into tumor microenvironment. NE P3 shape antitumor adaptive response breast melanoma. In this report, we demonstrate that cross-presented antigen PR1,...
Dephosphorylation of phosphatidic acid (PA) is the penultimate step in triglyceride synthesis. Adipocytes express soluble intracellular PA-specific phosphatases (Lipins) and broader specificity membrane-associated lipid phosphate (LPPs) that can also dephosphorylate PA. Inactivation lipin1 causes lipodystrophy mice due to defective developmental adipogenesis. Triglyceride synthesis diminished but not ablated by inactivation differentiated adipocytes implicating other PA this process. To...