A5049499841- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Neutropenia and Cancer Infections
- Colorectal Cancer Treatments and Studies
- Atherosclerosis and Cardiovascular Diseases
- IL-33, ST2, and ILC Pathways
- Diagnosis and treatment of tuberculosis
- Psoriasis: Treatment and Pathogenesis
- Cancer Genomics and Diagnostics
- Underwater Vehicles and Communication Systems
- interferon and immune responses
- Genetic factors in colorectal cancer
- Cytokine Signaling Pathways and Interactions
- Immunodeficiency and Autoimmune Disorders
- Chemokine receptors and signaling
- Marine and Offshore Engineering Studies
- Offshore Engineering and Technologies
- Virology and Viral Diseases
- SARS-CoV-2 and COVID-19 Research
- Immune Response and Inflammation
- Diabetes and associated disorders
- Lung Cancer Research Studies
Providence Portland Medical Center
2018-2024
Benaroya Research Institute
2011-2020
Leiden University Medical Center
2019
St. Joseph Health System
2019
Providence College
2019
University of Washington
2012-2017
Behavioral Tech Research, Inc.
2014
Inserm
2007-2010
Université Claude Bernard Lyon 1
2007-2010
Hospices Civils de Lyon
2007
Abstract Identifying tumor antigen-specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. Here, we show that CD103 + CD39 tumor-infiltrating CD8 (CD8 TIL) are enriched tumor-reactive both in primary metastatic tumors. This TIL subset is found across six different malignancies displays an exhausted tissue-resident memory phenotype. TILs have a distinct T-cell receptor (TCR) repertoire, with clones expanded the but present at low...
Human blood and lymph contain circulating CD4 + CD103 cutaneous resident memory T cells that can seed distant skin sites. See the related Focus by Carbone Gebhardt .
The enormous diversity of the naive T cell repertoire is instrumental in generating an immune response to virtually any foreign antigen that can be processed into peptides bind MHC molecules. low frequency antigen-specific cells, their high activation threshold, and constrains antigen-processing presentation have hampered analysis repertoires complex protein antigens. In this study, libraries polyclonally expanded cells were used determine dose–response human CD4+ specific for a variety...
In humans, Th1/17 cells, identified by coexpression of the chemokine receptors CCR6 and CXCR3, are proposed to be highly pathogenic in several autoimmune disorders due part their expression proinflammatory cytokines IL-17, IFN-γ, GM-CSF. However, developmental requirements, relationship with "classic" Th17 Th1 cells physiological role normal immune responses not well understood. this study, we examined CCR6+ CXCR3+ from healthy individuals found that ex vivo these produced effector IL-22,...
CD4+ Th cells play a key role in orchestrating immune responses, but the identity of involved antitumor response remains to be defined. We analyzed cell infiltrates head and neck squamous carcinoma colorectal cancers identified subset distinct from FOXP3+ Tregs that coexpressed programmed death 1 (PD-1) ICOS. These tumor-infiltrating lymphocyte (CD4+ TILs) had tissue-resident memory phenotype, were present MHC class II-rich areas, proliferated tumor, suggesting local antigen recognition. The...
Multiple sclerosis is an inflammatory T cell-mediated autoimmune disease. In a Phase II clinical trial, high-dose immunosuppressive therapy combined with autologous CD34+ haematopoietic stem cell transplant resulted in 69·2% of subjects remaining disease-free without evidence relapse, loss neurological function or new magnetic resonance imaging (MRI) lesions to year 5 post-treatment. A combination CyTOF mass cytometry and multi-parameter flow was used explore the reconstitution kinetics...
Abstract Background The efficacy of checkpoint blockade immunotherapies in colorectal cancer is currently restricted to a minority patients diagnosed with mismatch repair-deficient tumors having high mutation burden. However, this observation does not exclude the existence neoantigen-specific T cells cancers low burden and exploitation their anti-cancer potential for immunotherapy. Therefore, we investigated whether autologous cell responses could also be observed repair-proficient cancers....
Abstract After activation, CD4+ Th cells differentiate into functionally specialized populations that coordinate distinct immune responses and protect against different types of pathogens. In humans, these effector memory cell subsets can be readily identified in peripheral blood based on their differential expression chemokine receptors govern homeostatic inflammatory trafficking. Foxp3+ regulatory T (Treg) also divided phenotypically mirror each share key transcription factors cytokines....
Background Expression of CD103 and CD39 has been found to pinpoint tumor-reactive CD8 + T cells in a variety solid cancers. We aimed investigate whether these markers specifically identify neoantigen-specific colorectal cancers (CRCs) with low mutation burden. Experimental design Whole-exome RNA sequencing 11 mismatch repair-proficient (MMR-proficient) CRCs corresponding healthy tissues were performed determine the presence putative neoantigens. In parallel, tumor-infiltrating lymphocytes...
Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses applied in veterinary vaccination explored as candidate vaccines for humans. However, express multiple genes encoding proteins that interfere with components the innate adaptive immune response. This manuscript describes two strategies aimed to improve immunogenicity highly attenuated, host-range restricted poxvirus NYVAC: deletion viral gene type-I interferon-binding protein development attenuated...
Tissue resident memory (Trm) CD8 T cells infiltrating tumors represent an enriched population of tumor antigen-specific cells, and their presence is associated with improved outcomes in patients. Using genetically engineered mouse pancreatic models we demonstrate that implantation generates a Trm niche dependent on direct antigen presentation by cancer cells. However, observe initial CCR7-mediated localization to draining lymph nodes required subsequently generate CD103+ tumors. We the...
Measles virus (MeV) infection is characterized by the formation of multinuclear giant cells (MGC). We report that beta interferon (IFN-beta) production amplified in vitro virus-induced MGC derived from human epithelial or mature conventional dendritic cells. Both fusion and IFN-beta response amplification were inhibited a dose-dependent way fusion-inhibitory peptide after MeV This effect was observed at both low high multiplicities infection. While absence replication, cell-cell mediated H/F...
CD4+ T-cell subsets play a major role in the host response to infection, and healthy immune system requires fine balance between reactivity tolerance. This is part maintained by regulatory T cells (Treg), which promote tolerance, loss of tolerance contributes autoimmunity. As drive immunity are diverse, identifying understanding how these function specific biomarkers. From human CD4 Tconv/Treg cell genome wide analysis we identified peptidase inhibitor 16 (PI16) as subset biomarker now show...
The T cell-dependent differentiation and function of B lymphocytes are tightly regulated by TNF ligands (L) receptors interactions, such as CD40/CD40L, CD27/CD70 CD134/CD314L. LIGHT/HVEM system [homologous to lymphotoxin, inducible expression, competing for GpD herpes virus, that binds the virus entry mediator (HVEM), is expressed on activated lymphocytes) focused our attention since HVEM has a large distribution that, in addition cells, DC or NK, includes tumor normal lymphocytes. was...
6011 Background: This phase Ib clinical trial was performed to investigate an agonistic murine antibody OX40 (MEDI6469) at various dose intervals prior definitive surgical resection in patients with head and neck squamous cell carcinoma (HNSCC). Methods: 17 resectable stage III-IVA HNSCC (11 = HPV-; 7 HPV+) received MEDI6469 0.4mg/kg x 3 doses administered on day 1, 3-4 5-6 of the study, followed by excision dissection either 2 days, 1 week or weeks after infusion anti-OX40. Primary tumor,...
Background Multidrug resistance-1 (MDR1) transporter limits the intracellular accumulation of chemotherapies (paclitaxel, anthracyclines) used in breast cancer (BC) treatment. In addition to tumor cells, MDR1 is expressed on immune cell subsets which it confers chemoresistance. Among human T by most CD8 + and a subset CD4 helper (Th) cells. Here we explored expression, function regulation cells investigated role this population response neoadjuvant chemotherapy (NAC) BC. Methods Phenotypic...
Abstract Depending on the activation status, plasmacytoid dendritic cells (PDC) and myeloid DC have ability to induce CD4 T cell development toward helper type 1 (Th1) or Th2 pathways. Thus, we tested whether different signals could also an impact profile of chemokines produced by human PDC. Signals that PDC promote a response (i.e., viruses) 2 [i.e., CD40 ligand (CD40L)] induced isolated from tonsils secrete preferentially attracting Th1 [such as interferon-γ (IFN-γ)-inducible protein...
Blockade of NKG2A/HLA-E interaction is a promising strategy to unleash the anti-tumor response. Yet role NKG2A+ CD8 T cells in response and regulation NKG2A expression on human tumor-infiltrating are still poorly understood. Here, by performing CITE-seq derived from head neck squamous cell carcinoma colorectal cancer, we show that induced differentiating into cytotoxic, CD39+CD103+ double positive (DP) cells, phenotype associated with tumor-reactive cells. This developmental trajectory leads...