A5026853463- Acute Myeloid Leukemia Research
- CAR-T cell therapy research
- Multiple Myeloma Research and Treatments
- Cancer Research and Treatments
- Hematopoietic Stem Cell Transplantation
- Histone Deacetylase Inhibitors Research
- Immune Cell Function and Interaction
- Acute Lymphoblastic Leukemia research
- Lymphoma Diagnosis and Treatment
- Neutropenia and Cancer Infections
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Immunotherapy and Biomarkers
- Protein Degradation and Inhibitors
- CNS Lymphoma Diagnosis and Treatment
- Axon Guidance and Neuronal Signaling
- Chronic Myeloid Leukemia Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- T-cell and B-cell Immunology
- Pericarditis and Cardiac Tamponade
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Single-cell and spatial transcriptomics
- T-cell and Retrovirus Studies
The University of Texas MD Anderson Cancer Center
2022-2025
UPMC Hillman Cancer Center
2017-2025
University of Pittsburgh
2018-2025
University of Pittsburgh Medical Center
2016-2023
Tsinghua University
2021
UPMC Health System
2016-2019
McGowan Institute for Regenerative Medicine
2018
National and Kapodistrian University of Athens
2012-2013
Abstract CD8 + T cells are critical mediators of antitumor immunity but differentiate into a dysfunctional state, known as cell exhaustion, after persistent receptor stimulation in the tumor microenvironment (TME). Exhausted (T ex ) characterized by upregulation coinhibitory molecules and reduced polyfunctionality. TME experience an immunosuppressive metabolic environment via levels nutrients oxygen buildup lactic acid. Here we show that terminally uniquely upregulate Slc16a11 , which...
Results following hematopoietic stem cell transplantation (HSCT) for TP53-mutated myeloid malignancies are disappointing. Several HSCT centers decline to perform patients with TP53 mutation because of poor outcomes. In this study, we analyzed 240 myelodysplastic syndrome (MDS) or acute leukemia (AML) that underwent HSCT. We aimed identify the benefit most from The primary outcome was progression-free survival (PFS). Fifty-two percent cohort had AML and median age 62. MDS outcomes were...
Response rates to immunotherapy in solid tumors remain low due part the elevated prevalence of terminally exhausted T cells, a hypofunctional differentiation state induced through persistent antigen and stress signaling. However, mechanisms promoting progression terminal exhaustion tumor undefined. Using low-input chromatin immunoprecipitation sequencing method CUT&RUN, we profiled histone modification landscape tumor-infiltrating CD8+ cells throughout differentiation. We found that had...
Cellular immunotherapies for cancer represent a means by which patient's immune system can be augmented with high numbers of tumor-specific T cells. Chimeric antigen receptor (CAR) therapy involves genetic engineering to 'redirect' peripheral cells tumor targets, showing remarkable potency in blood cancers. However, due several resistance mechanisms, CAR-T cell therapies remain ineffective solid tumors. We and others have shown the microenvironment harbors distinct metabolic landscape that...
While checkpoint blockade immunotherapies have widespread success, they rely on a responsive immune infiltrate; as such, treatments enhancing infiltration and preventing immunosuppression are of critical need. We previously generated αPD-1 resistant variants the murine HNSCC model MEER. entirely resistant, these tumors regress after single dose oncolytic vaccinia virus (VV). then VV-resistant MEER line to dissect immunologic features sensitive tumors. treatment both tumor types induced IFNγ,...
ABSTRACT Key osteoclast (OCL) regulatory gene promoters in bone marrow–derived monocytes harbor bivalent histone modifications that combine activating Histone 3 lysine 4 tri-methyl (H3K4me3) and repressive H3K27me3 marks, which upon RANKL stimulation resolve into or architecture. Enhancer of zeste homologue 2 (EZH2) is the methyltransferase component polycomb complex 2, catalyzes modifications. Immunofluorescence microscopy reveals EZH2 localization during murine osteoclastogenesis...
Abstract Nutrient stress represents a significant barrier for antitumor immunity, and tumor interstitial fluid (TIF) often contains metabolites that hinder immune function. However, it is difficult to isolate the effects of nutrient from other suppressive factors. Thus, we employed chemically-defined cell culture medium based on metabolomic profile TIF: Tumor Interstitial Fluid Medium (TIFM). Culture CD8 + T cells in TIFM limited expansion impaired effector functions upon restimulation,...
Primary urinary tract lymphoma (PUTL) is an uncommon disease with only a few case reports in the literature.
Abstract Acute myeloid leukemia (AML) in older patients has a poor prognosis, low complete remission (CR) rates, and overall survival (OS). Preclinical studies have shown synergistic effects of epigenetic priming with hypomethylating agents followed by cytarabine. Based on these data, we hypothesized that an induction regimen using decitabine, cytarabine would be effective safe previously untreated AML. Here, conducted phase 2 trial which AML received consisting 1 or courses decitabine 20...
When multiple haploidentical donors are available for transplantation, those of younger generations generally selected over older generations. However, it is unclear who the optimal donor when selecting candidates from within a generation, such as father versus mother, son daughter, or brother sister. Although traditionally male favored female donors, particularly recipients, and significant associations individual HLA mis(matches) on outcomes being increasingly recognized, hierarchy factors...
The modeling of chimeric antigen receptor (CAR) T cell therapies has been mostly focused on immunodeficient models. However, there are many advantages in studying CAR-T biology an immunocompetent setting. We generated a fully murine CAR targeting CD105 (endoglin), component the TGFβ expressed surface certain solid tumors and acute leukemias. CD105-targeted cells can be grown from various backgrounds, tracked vivo by congenic marks, activated isolation or tumor cells. were toxic at higher...
Leukemia relapse 5 years after achieving first complete remission (CR1) is uncommon in patients with acute myeloid leukemia (AML). In this study, we evaluated the outcomes of AML late at our institution and reviewed literature for these patients. The study cohort consisted nine relapse. median interval between CR1 was 6.1 (range: 5.116.2 years). At relapse, karyotype different from initial diagnosis 50% time seven received induction chemotherapy two hypomethylating agents an overall CR rate...
Acute myeloid leukaemia (AML) is conventionally thought of as a medical emergency. However, several studies on the association time from diagnosis to treatment with survival did not have concordant results. Here we analyse 55 985 AML patients National Cancer Database, and show that in less than 60 years old five-day delay chemotherapy initiation leads worse long-term survival. The difference small [hazard ratio (HR) 1.05, 95% confidence interval (CI) 1.01-1.09 multivariate analysis] but...
The aim of the present study was to estimate risk therapy-related acute myeloid leukemia (t-AML) in patients with gynecologic malignancies receiving chemotherapy using a population-based database.The National Cancer Institute's Surveillance, Epidemiology, and End Results database accessed, cohort women diagnosed primary ovarian, uterine, or cervical malignancy between January 1, 1992, December 31, 2014, who received selected. Those subsequently developed AML were identified. Standardized...