A5071750923- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Immune cells in cancer
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- Virus-based gene therapy research
- MicroRNA in disease regulation
- Galectins and Cancer Biology
- Phagocytosis and Immune Regulation
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Viral Infectious Diseases and Gene Expression in Insects
- TGF-β signaling in diseases
- Glycosylation and Glycoproteins Research
- Single-cell and spatial transcriptomics
- interferon and immune responses
- Cell Adhesion Molecules Research
- Chemokine receptors and signaling
- Histone Deacetylase Inhibitors Research
- Cutaneous lymphoproliferative disorders research
- Lymphoma Diagnosis and Treatment
Moffitt Cancer Center
2018-2025
Duke University
2023-2025
Duke Cancer Institute
2023-2024
Duke Medical Center
2024
Institut d'Investigació Biomédica de Bellvitge
2015-2017
Universidad de Salamanca
2012
Tumor-associated macrophages are major contributors to malignant progression and resistance immunotherapy, but the mechanisms governing their differentiation from immature myeloid precursors remain incompletely understood. In this study, we demonstrate that exosomes secreted by human mouse tumor-educated mesenchymal stem cells (MSCs) drive accelerated breast cancer inducing of monocytic myeloid-derived suppressor into highly immunosuppressive M2-polarized at tumor beds. Mechanistically,...
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
Abstract Understanding the intrinsic mediators that render CD8 + T cells dysfunctional in tumor microenvironment is a requirement to develop more effective cancer immunotherapies. Here, we report C/EBP homologous protein (Chop), downstream sensor of severe endoplasmic reticulum (ER) stress, major negative regulator effector function tumor-reactive cells. Chop expression increased tumor-infiltrating cells, which correlates with poor clinical outcome ovarian patients. Deletion improves...
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,...
The introduction of new therapies against particular genetic mutations in non-small-cell lung cancer is a promising avenue for improving patient survival, but the target population small. There need to discover potential actionable lesions, which end, non-conventional pathways, such as RNA editing, are worth exploring. Herein we show that adenosine-to-inosine editing enzyme ADAR1 undergoes gene amplification non-small cell lines and primary tumors association with higher levels corresponding...
Farnesoid X receptor (FXR) has been recently reported to enhance chemoresistance through bile acid-independent mechanisms. Thus, FXR transfection plus activation with GW4064 resulted in reduced sensitivity cisplatin-induced toxicity. This is interesting because primary tumors of the liver, an organ where expressed, exhibit marked refractoriness pharmacological treatment. Here we have determined whether upregulated hepatocellular carcinoma (HCC), cholangiocarcinoma (CGC) and hepatoblastoma...
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
Myeloid-derived suppressor cells (MDSC) represent a primary mechanism of immune evasion in tumors and have emerged as major obstacle for cancer immunotherapy. The immunoinhibitory activity MDSC is tightly regulated by the tumor microenvironment occurs through mechanistic mediators that remain unclear. Here, we elucidated intrinsic interaction between expression AMP-activated protein kinase alpha (AMPKα) immunoregulatory tumors. AMPKα signaling was increased tumor-MDSC from tumor-bearing mice...
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...
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,...
Immuno-oncology has traditionally focused on conventional MHC-restricted αβ T cells. Yet, unconventional γδ cells, which kill tumor cells in an MHC-unrestricted manner, display characteristics of effector activity and stemness without exhaustion are nearly universally observed human gynecologic malignancies, correlating with improved outcomes. These do not have a clear counterpart mice but also found the healthy female reproductive tract. Interventions that modulate their vivo activity, or...
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.