Thomas McKee

ORCID: 0000-0002-2147-3136
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About
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Research Areas
  • CAR-T cell therapy research
  • Genetic factors in colorectal cancer
  • Monoclonal and Polyclonal Antibodies Research
  • Cancer Genomics and Diagnostics
  • Immune Cell Function and Interaction
  • Virus-based gene therapy research
  • T-cell and B-cell Immunology
  • Immunotherapy and Immune Responses
  • Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Chemokine receptors and signaling
  • Immune cells in cancer
  • Melanoma and MAPK Pathways
  • Pancreatic and Hepatic Oncology Research
  • Colorectal Cancer Treatments and Studies
  • PARP inhibition in cancer therapy
  • Viral Infections and Immunology Research
  • Cancer Immunotherapy and Biomarkers
  • Cell Adhesion Molecules Research
  • Herpesvirus Infections and Treatments
  • Lymphoma Diagnosis and Treatment
  • Proteoglycans and glycosaminoglycans research
  • Viral gastroenteritis research and epidemiology
  • Lung Cancer Treatments and Mutations
  • Peptidase Inhibition and Analysis
  • DNA Repair Mechanisms

University of Geneva
2008-2024

University Hospital of Geneva
2015-2024

Swiss Cancer Center Léman
2024

Geneva College
2009-2024

Hôpital Beau-Séjour
2020-2023

Thomas Jefferson University Hospital
2019

Health Net
2018

Light Chain Bioscience (Switzerland)
2012

University of Lausanne
2004-2006

Tulane University
2006

Tumor microenvironments (TMEs) influence cancer progression but are complex and often differ between patients. Considering that microenvironment variations may reveal rules governing intratumoral cellular programs disease outcome, we focused on tumor-to-tumor variation to examine 52 head neck squamous cell carcinomas. We found macrophage polarity-defined by

10.1126/science.ade2292 article EN Science 2023-08-03

Abstract In human cutaneous malignant melanoma, a predominance of activated mutations in the N-ras gene has been documented. To obtain mouse model most closely mimicking disease, transgenic line was generated by targeting expression dominant-active (N-RasQ61K) to melanocyte lineage tyrosinase regulatory sequences (Tyr::N-RasQ61K). Transgenic mice show hyperpigmented skin and develop metastasizing melanoma. Consistent with tumor suppressor function INK4a locus that encodes p16INK4A p19ARF,...

10.1158/0008-5472.can-04-2970 article EN Cancer Research 2005-05-15

A herpes simplex virus mutant, in1814, possessing a 12-base-pair insertion in the gene encoding transinducing factor Vmw65 has been constructed. The abolished ability of to transinduce immediate-early (IE) expression and form protein-DNA complex with cell proteins IE-specific regulatory element TAATGAGAT. Accumulation IE RNA 1 2 was reduced four- fivefold in1814-infected cells, but level 4 only by twofold, 3 unaffected. Mutant in1814 had high particle/PFU ratio, many particles, although...

10.1128/jvi.63.5.2260-2269.1989 article EN Journal of Virology 1989-05-01

The bone marrow constitutes a favorable environment for long-lived antibody-secreting plasma cells, providing blood-circulating antibody. Plasma cells are also present in mucosa-associated lymphoid tissue (MALT) to mediate local frontline immunity, but how cell survival there is regulated not known. Here we report that proliferation-inducing ligand (APRIL) promoted of human upper and lower MALT by upregulating expression the antiapoptotic proteins bcl-2, bcl-xL, mcl-1. situ localization...

10.1172/jci33760 article EN Journal of Clinical Investigation 2008-07-01

We have previously demonstrated that induction of antiviral cytotoxic T lymphocytes (CTL), in the absence antibodies, can confer protection against a lethal-dose virus challenge. Here we extend those findings as follows. First, three discrete viral CTL epitopes expressed from minigenes encoding peptides short 12 amino acids be recognized when recombinant vaccinia virus; second, concentrating on two epitopes, show these recombinants major histocompatibility complex (MHC)-restricted manner;...

10.1128/jvi.67.1.348-352.1993 article EN Journal of Virology 1993-01-01

Infants with severe primary combined immunodeficiency (SCID) and children post-allogeneic hematopoietic stem cell transplantation (HSCT) are extremely susceptible to unusual infections. The lack of generic tools detect disease-causing viruses among more than 200 potential human viral pathogens represents a major challenge clinicians virologists. We investigated retrospectively the causes fatal disseminated infection meningoencephalitis in an infant gamma C-SCID chronic gastroenteritis 2...

10.1371/journal.pone.0027483 article EN cc-by PLoS ONE 2011-11-11

ABSTRACT The glycosylphosphatidylinositol (GPI)-anchored complement regulatory protein decay-accelerating factor (DAF) is used by a number of enteroviruses as receptor during infection. DAF and other GPI-anchored proteins can be found in cholesterol-rich ordered domains within the plasma membrane that are known “lipid rafts.” We have shown, using drugs to specifically inhibit various endocytosis routes, infection DAF-using strain echovirus 11 (EV11) dependent upon cholesterol an intact...

10.1128/jvi.76.18.9307-9322.2002 article EN Journal of Virology 2002-09-15

SMAD4 loss is associated with the development of metastases and poor prognosis. We evaluated expression protein its association tumor characteristics, including biomarkers outcome in terms relapse-free survival overall survival.We used 1,564 stage II/III colon cancer samples from PETACC-3 to evaluate by immunohistochemistry. was validated assessing mRNA using available array data. also studied on 34 adenomas 10 liver their primaries. Loss immunoreactivity defined as focal or diffuse. Cases...

10.1158/1078-0432.ccr-15-0939 article EN Clinical Cancer Research 2016-02-10

Tumor-infiltrating neutrophils have been implicated in malignant development and progression, but mechanisms are ill defined. Neutrophils produce a proliferation-inducing ligand APRIL/TNFSF13, factor that promotes of tumors from diverse origins, including diffuse large B-cell lymphoma (DLBCL). High APRIL expression DLBCL correlates with reduced patient survival, the pathway(s) dictating not known. Here, we show all blood constitutively secrete APRIL, inflammation-associated stimuli, such as...

10.1158/0008-5472.can-16-0786 article EN Cancer Research 2016-12-07

Chordoma is a rare tumor of notochordal origin, currently principally treated by surgery and/or irradiation. Here, we describe the clinical outcome 3 consecutive patients with metastatic and locally advanced chordoma, different immunotherapeutic approaches. All presented fast growing tumors failure standard therapies. One was tumor-based vaccine, 2 others anti-PD1 antibodies, all impressive radiological responses. We therefore propose that chordoma an immunogenic thus translational research...

10.1080/2162402x.2017.1338235 article EN OncoImmunology 2017-06-21

The efficiency of the Myriad Homologous Recombination Deficiency (HRD) test to guide use poly (ADP-ribose) polymerase (PARP) inhibitors has been demonstrated in several phase III trials. However, a need exists for alternative clinically validated tests.A novel biomarker HRD was developed using Cancer Genome Atlas database and, as part ENGOT European Initiative, applied 469 samples from PAOLA-1/ENGOT-ov25 trial. Results were compared with myChoice Genomic Instability Score (GIS) respect...

10.1200/po.22.00555 article EN cc-by-nc-nd JCO Precision Oncology 2023-06-26

The functions of molecular chaperones have been extensively investigated biochemically in vitro and genetically bacteria yeast.We embarked on a functional genomic analysis the Hsp90 chaperone machine mouse by disrupting p23 gene using trap approach.p23 is an cochaperone that thought to stabilize Hsp90-substrate complexes and, independently, act as cytosolic prostaglandin E2 synthase.Gene deletions budding fission yeasts knock-down experiments with worm not revealed any clear vivo...

10.1128/mcb.00734-06 article EN Molecular and Cellular Biology 2006-11-15

BACKGROUND The distinction between adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA) on fine‐needle aspiration biopsy (FNAB) can be challenging. Recently, a specific translocation t(6;9) involving the v‐myb avian myeloblastosis viral oncogene homolog ( MYB ) nuclear factor I/B NFIB genes was identified in ACCs, which it contributes to overexpression. authors investigated use of immunocytochemistry FNAB specimens as an ancillary test for cytologic diagnosis ACC. METHODS expression...

10.1002/cncy.21381 article EN Cancer Cytopathology 2013-12-02

Immuno-oncology is an ever growing field that has seen important progress across the spectrum of cancers. Responses can be deep and durable. However, as only a minority patients respond to checkpoint inhibition, predictive biomarkers are needed. Cancer genetic disease arising from accumulation somatic mutations in DNA affected cells. Tumor mutational burden (TMB), represents number tumor form neoantigens, responsible for immunogenicity tumors. Randomized controlled trials have so far failed...

10.3389/fonc.2020.00142 article EN cc-by Frontiers in Oncology 2020-02-12

PURPOSE Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown promising clinical results in the treatment of ovarian cancer. Analysis biomarker subgroups consistently revealed higher benefits for patients with homologous recombination deficiency (HRD). The test that is most often used detection HRD studies Myriad myChoice assay. However, other assays can also be to assess biomarkers, which are indicative HRD, genomic instability (GI), and BRCA1/ 2 mutation status. Many these high...

10.1200/po.23.00348 article EN cc-by-nc-nd JCO Precision Oncology 2024-03-01

Acute myeloid leukemia (AML) remains a challenging hematological malignancy with poor prognosis and limited treatment options. Leukemic stem cells (LSCs) contribute to therapeutic failure, relapse, adverse outcome. This study investigates the role of quiescence related molecular mechanisms in AML pathogenesis LSC functions identify potential targets. Transcriptomic analysis revealed that LSC-enriched quiescent cell population has distinct gene signature prognostic relevance patients AML....

10.1126/scitranslmed.adk1731 article EN Science Translational Medicine 2024-07-24

Abstract Abundant mRNA expression for a proliferation-inducing ligand (APRIL) from tumor necrosis factor (TNF) family is observed in many solid tumors. Here, we analyzed situ the cellular source of APRIL human tumors with anti-APRIL antibodies. In most cases, neutrophils present stroma constituted main APRIL. cutaneous lesions such as melanoma or basal cell carcinoma, tumor-adjacent keratinocytes also produced production by cells themselves was rare event, only urothelial bladder cancer and...

10.1189/jlb.1105655 article EN Journal of Leukocyte Biology 2006-06-22
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