A5079599192- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Cutaneous lymphoproliferative disorders research
- Galectins and Cancer Biology
- Glycosylation and Glycoproteins Research
- Cardiomyopathy and Myosin Studies
- Mast cells and histamine
- Dietary Effects on Health
- Fungal Infections and Studies
- Oral health in cancer treatment
- Immune cells in cancer
- Genomics and Phylogenetic Studies
- Cytomegalovirus and herpesvirus research
- Cancer survivorship and care
- Gut microbiota and health
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- Radiopharmaceutical Chemistry and Applications
Duke University
2023-2024
Duke Medical Center
2024
Moffitt Cancer Center
2018-2023
Duke Cancer Institute
2023
University of South Florida
2018
Abstract Most ovarian cancers are infiltrated by prognostically relevant activated T cells 1–3 , yet exhibit low response rates to immune checkpoint inhibitors 4 . Memory B cell and plasma infiltrates have previously been associated with better outcomes in cancer 5,6 but the nature functional relevance of these responses controversial. Here, using 3 independent cohorts that total comprise 534 patients high-grade serous cancer, we show robust, protective humoral dominated production...
The immune checkpoint receptor PD-1 on T follicular helper (Tfh) cells promotes Tfh:B cell interactions and appropriate positioning within tissues. Here, we examined the impact of regulation expression by genomic organizer SATB1 Tfh differentiation. Vaccination CD4CreSatb1f/f mice enriched for antigen-specific cells, TGF-β-mediated repression enhanced differentiation human cells. Mechanistically, high Icos in Satb1-/- CD4+ promoted preventing regulatory skewing resulted increased...
Despite repeated associations between T cell infiltration and outcome, human ovarian cancer remains poorly responsive to immunotherapy. We report that the hallmarks of tumor recognition in cancer-infiltrating cells are primarily restricted tissue-resident memory (TRM) cells. Single-cell RNA/TCR/ATAC sequencing 83,454 CD3
BTN3A1 governs antitumor responses T lymphocytes are immune cells that can be activated through their gamma delta (γδ) or alpha beta (αβ) receptors. Both cell types found in human cancers, but current immunotherapies do not harness coordinated activity. Payne et al. and BTN2A1, two members of the butyrophilin family proteins, partner to activate most abundant subset γδ peripheral blood. Antibodies targeting redirect attack cancer while also increasing activity tumor-specific αβ cells. Thus,...
Abstract Due to their cytotoxic activities, many anticancer drugs cause extensive damage the intestinal mucosa and have antibiotic activities. Here, we show that cisplatin induces significant changes in repertoire of commensal bacteria exacerbate mucosal damage. Restoration microbiota through fecal-pellet gavage drives healing cisplatin-induced Bacterial translocation blood stream is correspondingly abrogated, resulting a reduction systemic inflammation, as evidenced by decreased serum IL-6...
Recent studies suggest that B cells could play an important role in the tumor microenvironment. However, of humoral responses endometrial cancer remains insufficiently investigated. Using a cohort 107 patients with different histological subtypes carcinoma, we evaluated coordinated and cellular adaptive immune cancer. Concomitant accumulation T, B, plasma at beds predicted better survival. only B-cell markers corresponded prolonged survival specifically high-grade endometrioid type serous...
Dimeric IgA (dIgA) can move through cells via the IgA/IgM polymeric immunoglobulin receptor (PIGR), which is expressed mainly on mucosal epithelia. Here, we studied ability of dIgA to target commonly mutated cytoplasmic oncodrivers. Mutation-specific dIgA, but not IgG, neutralized KRAS
Abstract Although chimeric antigen receptor (CAR)-expressing T cells have proven success in hematologic malignancies, their effectiveness solid tumors has been largely unsuccessful thus far. We found that some olfactory receptors are expressed a variety of different histologic subtypes, with limited pattern expression normal tissues. Quantification OR2H1 by qRT-PCR and Western blot analysis 17 tissues, 82 ovarian cancers various histologies, eight non–small cell lung (NSCLCs), breast...
Chemolithoautotrophic bacteria from the genera Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira are common, sometimes dominant, isolates sulfidic habitats including hydrothermal vents, soda salt lakes marine sediments. Their genome sequences confirm their membership in a deeply branching clade of Gammaproteobacteria. Several adaptations to heterogeneous apparent. genomes include large numbers genes for sensing responding environment (EAL- GGDEF-domain proteins methyl-accepting chemotaxis...
Abstract The pathogenesis of cutaneous T-cell lymphoma (CTCL) remains unclear. Using single-cell RNA or receptor (TCR) sequencing 32 619 CD3+CD4+ and CD26+/CD7+ 29 932 CD26−/CD7− lymphocytes from the peripheral blood 7 patients with CTCL, coupled to ATAC-sequencing 26,411 33 841 lymphocytes, we show that tumor cells in Sézary syndrome mycosis fungoides (MF) exhibit different phenotypes trajectories differentiation. When compared MF, narrower repertoires TCRs clonal enrichment. Surprisingly,...
Cutaneous T cell lymphoma (CTCL) has a poorly understood etiology and no known cure. Using conditional knockout mice, we found that ablation of the genomic organizer special AT-rich sequence-binding protein 1 (Satb1) caused malignant transformation mature, skin-homing, Notch-activated CD4+ CD8+ cells into progressively fatal lymphoma. Mechanistically, Satb1 restrained Stat5 phosphorylation expression skin-homing chemokine receptors in mature cells. Notably, methyltransferase-dependent...
To demonstrate that shared antibody responses in endometriosis and endometriosis-associated ovarian cancer spontaneously antagonize malignant progression can be leveraged to develop future immunotherapies.
Supplementary Data from Olfactory Receptor OR2H1 Is an Effective Target for CAR T Cells in Human Epithelial Tumors
Abstract Despite their long half-life, therapeutic antibodies are considered ineffective against intracellular antigens due to perceived inability penetrate epithelial cells. Using recombinant targeting common mutations in oncogenes, we have demonstrated that dimeric IgA, but not the same antibody on an IgG backbone, penetrates human cancer cells through PIGR-dependent directional transcytosis, specifically neutralizing mutated oncodrivers and expelling outside cell, bound secretory IgA....
Abstract Background- Treatment of metastatic head and neck cancer remains an area unmet need with median survival less than a year. We tested the efficacy novel circadian aligned fasting intervention called “time restricted eating” (TRE), to improve ICB response in tumor bearing syngeneic mice models (MOC1), showed significant reduction growth, which we then recapitulated pilot, open labeled, interventional clinical trial 30 patients. noted improvement progression free (5 months vs not...
Abstract γδ T cells, in contrast to the conventional MHC-restricted αβ, recognize and kill tumor cells an MHC-unrestricted manner, highlighting their potential for anti-tumor therapies. However, phenotypes of infiltrating human tumors role immunity remain poorly understood. To assess this, we characterized by Immuno-Seq/iRepertoire repertoire γδ-chains used intra-tumoral cancers from FACS-sorted freshly dissociated high-grade serous ovarian (HGSOCs), non-small cell lung cancer (NSCLC), small...
Abstract Chimeric Antigen Receptor (CAR) T cell therapy has proven to be successful in treating hematological malignancies. However, its effectiveness against solid tumors been suboptimal so far, due the strong immunosuppressive conditions and metabolic restrictions present tumor microenvironment. Furthermore, use of autologous cells for CAR product manufacturing several disadvantages. Here, we demonstrate a new platform using cord blood-derived γδ subsets, which can used allogeneically...
Abstract Chimeric antigen receptor (CAR) T cells have been successful for hematological malignancies, but so far showed limited efficiency against solid tumors. Olfactory receptors are expressed in a variety of epithelial cancers, with expression healthy tissues. We quantified olfactory OR2H1 ovarian cancer, non-small cell lung cancer (NSCLC), breast and many normal tissues, we found is multiple tumors to testis among human CAR targeting OR2H1-extracellular domain were generated,...
<div>Abstract<p>Recent studies suggest that B cells could play an important role in the tumor microenvironment. However, of humoral responses endometrial cancer remains insufficiently investigated. Using a cohort 107 patients with different histological subtypes carcinoma, we evaluated coordinated and cellular adaptive immune cancer. Concomitant accumulation T, B, plasma at beds predicted better survival. only B-cell markers corresponded prolonged survival specifically high-grade...
Supplementary Figure from IgA-Dominated Humoral Immune Responses Govern Patients' Outcome in Endometrial Cancer
Supplementary Figure from IgA-Dominated Humoral Immune Responses Govern Patients' Outcome in Endometrial Cancer
Supplementary Figure from IgA-Dominated Humoral Immune Responses Govern Patients' Outcome in Endometrial Cancer
Supplementary Figure from IgA-Dominated Humoral Immune Responses Govern Patients' Outcome in Endometrial Cancer
<div>Abstract<p>Recent studies suggest that B cells could play an important role in the tumor microenvironment. However, of humoral responses endometrial cancer remains insufficiently investigated. Using a cohort 107 patients with different histological subtypes carcinoma, we evaluated coordinated and cellular adaptive immune cancer. Concomitant accumulation T, B, plasma at beds predicted better survival. only B-cell markers corresponded prolonged survival specifically high-grade...