A5082626339- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Immune cells in cancer
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Nanoplatforms for cancer theranostics
- Melanoma and MAPK Pathways
- Advanced Breast Cancer Therapies
- Phagocytosis and Immune Regulation
- T-cell and B-cell Immunology
- Cancer, Hypoxia, and Metabolism
- HER2/EGFR in Cancer Research
- Cancer, Stress, Anesthesia, and Immune Response
- Cell Adhesion Molecules Research
- Cancer Research and Treatments
- Photodynamic Therapy Research Studies
- interferon and immune responses
- Tryptophan and brain disorders
- Cancer Cells and Metastasis
- Cancer Mechanisms and Therapy
- Bladder and Urothelial Cancer Treatments
- Epigenetics and DNA Methylation
- Ferroptosis and cancer prognosis
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
Weill Cornell Medicine
2023-2025
Cornell University
2013-2025
Swim Across America
2015-2024
Parker Institute for Cancer Immunotherapy
2016-2024
Memorial Sloan Kettering Cancer Center
2014-2023
Kettering University
2013-2023
New York Proton Center
2023
Case Western Reserve University
2019
Cleveland Clinic
2019
Memorial Hospital
2014
Abstract Tryptophan catabolism by the enzymes indoleamine 2,3-dioxygenase 1 and tryptophan 2 (IDO/TDO) promotes immunosuppression across different cancer types. The metabolite L-Kynurenine (Kyn) interacts with ligand-activated transcription factor aryl hydrocarbon receptor (AHR) to drive generation of Tregs tolerogenic myeloid cells PD-1 up-regulation in CD8 + T cells. Here, we show that AHR pathway is selectively active IDO/TDO-overexpressing tumors associated resistance immune checkpoint...
Abstract The major histocompatibility complex I (MHC-1) presents antigenic peptides to tumor-specific CD8+ T cells. regulation of MHC-I by kinases is largely unstudied, even though many patients with cancer are receiving therapeutic kinase inhibitors. Regulators cell-surface HLA amounts were discovered using a pooled human kinome shRNA interference–based approach. Hits scoring highly subsequently validated additional RNAi and pharmacologic MAP2K1 (MEK), EGFR, RET as negative regulators...
Ligation of GITR (glucocorticoid-induced tumor necrosis factor (TNF) receptor-related gene, or TNFRSF18) by agonist antibody has recently entered into early phase clinical trials for the treatment advanced malignancies. Although ability modulation to induce regression is well-documented in preclinical studies, underlying mechanisms action, particularly its effects on CD4(+)foxp3(+) regulatory T cells (Treg), have not been fully elucidated. We previously demonstrated that ligation vivo DTA-1...
Harnessing the adaptive immune response to treat malignancy is now a clinical reality. Several strategies are used melanoma; however, very few result in complete response. CD4+ T cells important and potent mediators of anti-tumor immunity adoptive transfer specific can promote tumor regression mice patients. OX40, costimulatory molecule expressed primarily on activated cells, promotes enhances with limited success large tumors mice. We show that OX40 engagement, context chemotherapy-induced...
Regulatory T cells (Tregs) suppress antitumor immunity by inhibiting the killing of tumor antigen-specific CD8+ cells. To better understand mechanisms involved, we used ex vivo three-dimensional collagen-fibrin gel cultures dissociated B16 melanoma tumors. This system recapitulated in suppression antimelanoma immunity, rendering resistant to cocultured activated, Immunosuppression was not observed when tumors excised from Treg-depleted mice were cultured this system. Experiments with...
Purpose: PD-1/PD-L1 pathway inhibition is effective against advanced renal cell carcinoma, although results are variable and may depend on host factors, including the tumor microenvironment. Vascular-targeted photodynamic (VTP) therapy with photosensitizer WST11 induces a defined local immune response, we sought to determine whether this could potentiate systemic antitumor response PD-1 inhibition.Experimental Design: Using an orthotopic Renca murine model of carcinoma that develops lung...
We describe a quantitative model for assessing the cytolytic activity of antigen-specific CD8+ T cells in vitro and vivo which concentration determines efficiency with these kill cognate antigen-expressing melanoma packed cell pellets, three-dimensional collagen-fibrin gels vitro, established melanomas vivo. In combination clonogenic assay cells, are 4,500-5,500-fold more sensitive than pellet-type assays generally used to measure activity. An equation previously neutrophil bactericidal also...
Tumor reliance on glycolysis is a hallmark of cancer. Immunotherapy more effective in controlling glycolysis-low tumors lacking lactate dehydrogenase (LDH) due to reduced tumor efflux and enhanced glucose availability within the microenvironment (TME). LDH inhibitors (LDHi) reduce uptake growth preclinical models, but their impact tumor-infiltrating T cells not fully elucidated. have higher basal expression levels compared with infiltrating cells, creating therapeutic opportunity for...
Phosphatidylserine (PS) is exposed on the surface of apoptotic cells and known to promote immunosuppressive signals in tumor microenvironment (TME). Antibodies that block PS interaction with its receptors have been shown repolarize TME into a proinflammatory state. Radiation therapy (RT) an effective focal treatment isolated solid tumors but less at controlling metastatic cancers. We found tumor-directed RT caused increase expression viable immune infiltrates mouse B16 melanoma. hypothesize...
Transcription factors ThPOK and Runx3 regulate the differentiation of “helper” CD4+ “cytotoxic” CD8+ T cell lineages respectively, inducing single positive (SP) cells that enter periphery with expression either CD4 or CD8 co-receptor. Despite expectation these fates are mutually exclusive mature CD4+CD8+ double (DP) present in healthy individuals augmented context disease, yet their molecular features pathophysiologic role disputed. Here, we show DP murine human tumors as a heterogenous...
Abstract Introduction: Multiple suppressive mechanisms within the tumor microenvironment (TME) contribute to blunt anti-tumor T cell responses. Among them, tumor-associated cells have been phenotypically described be functionally exhausted (or dysfunctional), reflecting a hyporesponsive state of chronically stimulated that express multiple inhibitory receptors immune checkpoint molecules), such as programmed death protein 1 (PD-1), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3),...