A5085317448- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Melanoma and MAPK Pathways
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- PI3K/AKT/mTOR signaling in cancer
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Immune cells in cancer
- MicroRNA in disease regulation
- Cutaneous Melanoma Detection and Management
- Tryptophan and brain disorders
- vaccines and immunoinformatics approaches
- Cancer Genomics and Diagnostics
- Virus-based gene therapy research
- COVID-19 Clinical Research Studies
- Gut microbiota and health
- Cancer Research and Treatments
- Retinoids in leukemia and cellular processes
- Ferroptosis and cancer prognosis
- Colorectal Cancer Treatments and Studies
- Bladder and Urothelial Cancer Treatments
University of Chicago
2016-2025
University of Chicago Medical Center
2011-2025
University of Illinois Chicago
2004-2023
University of Chicago Medicine Comprehensive Cancer Center
2020
Tennessee Oncology
2018
Fox Chase Cancer Center
2018
The Ohio State University
2018
Taiho Pharmaceutical (Japan)
2018
AstraZeneca (Poland)
2018
Varian Medical Systems (Germany)
2018
T cell infiltration of solid tumors is associated with favorable patient outcomes, yet the mechanisms underlying variable immune responses between individuals are not well understood. One possible modulator could be intestinal microbiota. We compared melanoma growth in mice harboring distinct commensal microbiota and observed differences spontaneous antitumor immunity, which were eliminated upon cohousing or after fecal transfer. Sequencing 16S ribosomal RNA identified Bifidobacterium as...
Anti-PD-1-based immunotherapy has had a major impact on cancer treatment but only benefited subset of patients. Among the variables that could contribute to interpatient heterogeneity is differential composition patients' microbiome, which been shown affect antitumor immunity and efficacy in preclinical mouse models. We analyzed baseline stool samples from metastatic melanoma patients before treatment, through an integration 16
Tumor escape from immune-mediated destruction has been associated with immunosuppressive mechanisms that inhibit T cell activation. Although evidence for an active immune response, including infiltration CD8(+) cells, can be found in a subset of patients, those tumors are nonetheless not immunologically rejected. In the current report, we show it is cell-inflamed showed high expression three defined mechanisms: indoleamine-2,3-dioxygenase (IDO), PD-L1/B7-H1, and FoxP3(+) regulatory cells...
T cell-mediated immunotherapies are promising cancer treatments. However, most patients still fail to respond these therapies. The molecular determinants of immune resistance poorly understood. We show that loss PTEN in tumor cells preclinical models melanoma inhibits killing and decreases T-cell trafficking into tumors. In patients, correlates with decreased infiltration at sites, reduced likelihood successful expansion from resected tumors, inferior outcomes PD-1 inhibitor therapy....
Spontaneous tumor-initiated T cell priming is dependent on IFN-β production by tumor-resident dendritic cells. On the basis of recent observations indicating that expression was upon activation host STING pathway, we hypothesized direct engagement through intratumoral (IT) administration specific agonists would result in effective anti-tumor therapy. After proof-of-principle studies using mouse agonist DMXAA showed a potent therapeutic effect, generated synthetic cyclic dinucleotide (CDN)...
Abstract Despite the frequent detection of circulating tumor antigen–specific T cells, either spontaneously or following active immunization adoptive transfer, immune-mediated cancer regression occurs only in minority patients. One theoretical rate-limiting step is whether effector cells successfully migrate into metastatic sites. Affymetrix gene expression profiling done on a series melanoma biopsies revealed major segregation samples based presence absence T-cell–associated transcripts....
A biphasic dose-response curve was observed when the IL-1-dependent HTL clone D10 exposed to IL-1 plus supernatants from some activated T cell clones but not others. The active component that inhibited proliferation at high concentrations of these appeared be IFN-gamma based on following findings: 1) pattern responsiveness correlated with presence in supernatants; 2) an anti-IFN-gamma mAb augmented cells 3) rIFN-gamma profoundly response stimulated rIL-1 supernatant or rIL-4; 4) rIL-2 also...
Abstract Although increased circulating tumor antigen-specific CD8+ T cells can be achieved by vaccination or adoptive transfer, progression nonetheless often occurs through resistance to effector function. To develop a model for identifying mechanisms of CTLs, poorly immunogenic B16-F10 melanoma was transduced express the Kb-binding peptide SIYRYYGL as green fluorescent protein fusion that should recognized high-affinity 2C TCR transgenic cells. B16.SIY expressed high levels antigen and...
Amplifications and mutations in the KIT proto-oncogene subsets of melanomas provide therapeutic opportunities.We conducted a multicenter phase II trial imatinib metastatic mucosal, acral, or chronically sun-damaged (CSD) melanoma with amplifications and/or mutations. Patients received 400 mg once per day twice if there was no initial response. Dose reductions were permitted for treatment-related toxicities. Additional oncogene mutation screening performed by mass spectroscopy.Twenty-five...
Abstract Purpose: The T-cell-inflamed phenotype correlates with efficacy of immune-checkpoint blockade, whereas non-T-cell-inflamed tumors infrequently benefit. Tumor-intrinsic WNT/β-catenin signaling mediates immune exclusion in melanoma, but association the tumor microenvironment other types is not well understood. Experimental Design: Using Cancer Genome Atlas (TCGA), a gene expression signature segregated samples within types. Activation was inferred using three approaches: somatic...
Purpose Stereotactic body radiotherapy (SBRT) may stimulate innate and adaptive immunity to augment immunotherapy response. Multisite SBRT is an emerging paradigm for treating metastatic disease. Anti-PD-1–treatment outcomes be improved with lower disease burden. In this context, we conducted a phase I study evaluate the safety of pembrolizumab multisite in patients solid tumors. Patients Methods progressing on standard treatment received two four metastases. Not all metastases were...
<h3>Background</h3> Blockade of immune inhibitory pathways is emerging as an important therapeutic modality for the treatment cancer. Single agent treatments have partial anti-tumor activity in preclinical models and human cancer patients. Inasmuch tumor microenvironment shows evidence multiple mechanisms present concurrently, it has been reasoned that combination therapies may be required optimal effect. <h3>Methods</h3> To test this notion, we utilized permutations anti-CTLA-4 mAb,...