A5009056123- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Chemokine receptors and signaling
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CRISPR and Genetic Engineering
- Pancreatic and Hepatic Oncology Research
- Pluripotent Stem Cells Research
- Immune cells in cancer
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer Research and Treatments
- Cancer Cells and Metastasis
- Phagocytosis and Immune Regulation
- Cancer Diagnosis and Treatment
- Biliary and Gastrointestinal Fistulas
- Gallbladder and Bile Duct Disorders
- Gastrointestinal disorders and treatments
- Single-cell and spatial transcriptomics
- Neuroendocrine Tumor Research Advances
- Cutaneous Melanoma Detection and Management
- Cancer Genomics and Diagnostics
- Hepatocellular Carcinoma Treatment and Prognosis
- Melanoma and MAPK Pathways
- Virus-based gene therapy research
USC Norris Comprehensive Cancer Center
2024-2025
Roswell Park Comprehensive Cancer Center
2016-2025
University of Southern California
2022-2025
University at Buffalo, State University of New York
2018-2023
Keck Hospital of USC
2023
LAC+USC Medical Center
2023
National Cancer Institute
2023
Jacobs (United States)
2021
Japan Broadcasting Corporation (Japan)
2018-2020
University of Michigan
2003-2020
Abstract Immune checkpoint inhibitors (ICI) have revolutionized treatment for various cancers; however, durable response is limited to only a subset of patients. Discovery blood-based biomarkers that reflect dynamic change the tumor microenvironment, and predict ICI, will markedly improve current regimens. Here, we investigate CX3C chemokine receptor 1 (CX3CR1), marker T-cell differentiation, as predictive correlate ICI therapy. Successful tumor-bearing mice with increases frequency...
In Brief Background: Hilar cholangiocarcinoma is an uncommon tumor with a poor prognosis. We sought to evaluate recurrence patterns and prognostic factors for disease-specific disease-free survival in patients surgically resected hilar single institution over the last 21 years. Methods: From 1985 2006, all referred tertiary surgical clinic were evaluated. Demographic data, characteristics, outcome analyzed retrospectively. Outcome was compared treated recent era (1995–2006) earlier...
Abstract The ability of cancer cells to ensure T-cell exclusion from the tumor microenvironment is a significant mechanism resistance anti-PD-1/PD-L1 therapy. Evidence indicates crucial roles Batf3-dependent conventional type-1 dendritic (cDC1s) for inducing antitumor immunity; however, strategies maximize cDC1 engagement remain elusive. Here, using multiple orthotopic mouse models resistant anti-PD-L1-therapy, we are testing hypothesis that in situ induction and activation tumor-residing...
Immune checkpoints (CTLA4 & PD-1) are inhibitory pathways that block aberrant immune activity and maintain self-tolerance. Tumors co-opt these to avoid destruction. checkpoint inhibitors (ICIs) activate cells restore their tumoricidal potential, making them highly efficacious cancer therapies. However, immunotolerant organs such as the liver depend on tolerogenic mechanisms, disruption with ICI use can trigger unintended side effect of hepatotoxicity termed immune-mediated injury from ICIs...
We have previously reported that adoptive transfer of tumor-draining lymph node (TDLN) B cells confers tumor regression in a spontaneous pulmonary metastasis mouse model breast cancer. In this study, we identified IL-10-producing within these cells, and found IL-10 removal, either by using IL-10(-/-) TDLN or systemic neutralization IL-10, significantly augmented the therapeutic efficacy adoptively transferred cells. Depletion B-cell transfers increased CTLs activity PBMCs splenic recipient....
Although blockade of the programmed cell death 1/programmed ligand 1 (PD-1/PD-L1) immune checkpoint has revolutionized cancer treatment, how it works on tumor-infiltrating CD8+ T cells recognizing same antigen at various differentiation stages remains elusive. Here, we found that chemokine receptor CX3CR1 identified 3 distinct states intratumor subsets. Adoptively transferred antigen-specific CX3CR1–CD8+ generated phenotypically and functionally CX3CR1int CX3CR1hi subsets in periphery....
Background Immune checkpoint inhibitors (ICI) have emerged as a front-line therapy for variety of solid tumors. With the widespread use these agents, immune-associated toxicities are increasingly being recognized, including fatal myocarditis. There limited data on outcomes and prognostic utility biomarkers associated with ICI-associated Our objective was to examine associations between clinical cardiomyocyte damage mortality in patients cancer treated ICIs. Methods We retrospectively studied...
Abstract In weakly and poorly immunogenic tumor models, we examined the effects of stimulating CD137 (4-1BB) in vivo by administering anti-CD137 monoclonal antibody after lysate-pulsed dendritic cell (TP-DC) vaccination. TP-DC subcutaneous vaccination induced a transient up-regulation on T cells natural killer (NK) within vaccine-primed lymph nodes (VPLNs). established pulmonary synergistically enhanced regression model, combined therapy resulted improved survival. Combined also local...
To determine the utility of routine perioperative bilateral internal jugular venous sampling parathyroid hormone (BIJ PTH) for localization during surgery.Venous PTH is a useful tool in patients undergoing reoperative surgery hyperparathyroidism (HPT). With development intraoperative rapid (ioPTH) testing, with ioPTH testing to guide operative has been shown be possible select, difficult cases. However, value BIJ HPT unclear.Between May 2004 and February 2006, 216 consecutive underwent neck...
Background Dendritic cells (DCs) play critical roles in regulating the innate and adaptive immune responses, have long been a major focus of cancer immunotherapy. Accumulating evidence suggests that conventional type 1 DCs (cDC1s) excel cross-presentation exogenous antigens on MHC-I molecules induction antitumor CD8 + T cell immunity; however, obtaining large numbers cDC1s is difficult. The use reprogramming differentiation technology advantageous for unlimited autologous especially...
Induced pluripotent stem cell (iPSC)-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers clinical translation. Our data indicate these iPSC-derived CD8 single-positive are more like CD4
Background Dendritic cells (DCs) are a promising therapeutic target in cancer immunotherapy given their ability to prime antigen-specific T cells, and initiate antitumor immune response. A major obstacle for DC-based is the difficulty obtain sufficient number of functional DCs. Theoretically, this limitation can be overcome by using induced pluripotent stem (iPSCs); however, strategies engage iPSC-derived DCs (iPSC-DCs) into remain elucidated. Accumulating evidence showing that induction...
Lack of reliable predictive biomarkers is a major limitation combination therapy with chemotherapy and anti–programmed cell death protein 1/programmed death-ligand 1 (anti-PD-1/PD-L1) (chemo-immunotherapy). We previously observed that the increase peripheral blood CD8+ T cells expressing CX3CR1, marker differentiation, correlates response to anti–PD-1 therapy; however, prognostic value T-cell CX3CR1 expression during chemo-immunotherapy unknown. Here, we evaluated utility circulating...
Abstract Compelling evidence shows that the frequency of T cells in tumor microenvironment correlates with prognosis as well response to immunotherapy. However, considerable heterogeneity exists within tumor-infiltrating cells, and significance their genomic transcriptomic landscape on clinical outcomes remains be elucidated. Signaling lymphocyte activation molecule 6 ( SLAMF6 ) is expressed intra-tumoral progenitor-exhausted which exhibit capacity proliferate, self-renew produce...
Purpose While surgical resection is a cornerstone of cancer treatment, local and distant recurrences continue to adversely affect outcome in significant proportion patients. Evidence that an alternative debulking strategy involving radiofrequency ablation (RFA) induces antitumor immunity prompted the current investigation efficacy performing RFA prior (pre-resectional RFA) preclinical mouse model. Experimental Design Therapeutic systemic immune responses were assessed following...
Current approaches to adoptive T-cell therapy are limited by the difficulty of obtaining sufficient numbers T cells against targeted antigens with useful in vivo characteristics. Theoretically, this limitation could be overcome using induced pluripotent stem (iPSC) that provide an unlimited source autologous cells. However, therapeutic efficacy iPSC-derived regenerated remains demonstrated. Here, we report first successful reprogramming receptor (TCR) transgenic CD8(+) into pluripotency. As...
Abstract Melanoma brain metastases (MBM) are clinically challenging to treat and exhibit variable responses immune checkpoint therapies. Prior research suggests that MBM poor tumor enriched in oxidative phosphorylation. Here, we report results from a multi-omic analysis of large, real-world melanoma cohort. exhibited lower interferon-gamma (IFNγ) scores T cell-inflamed compared primary cutaneous (PCM) or extracranial (ECM), which was independent mutational burden. Among MBM, there were fewer...
Evidence has shown that T-cell receptors (TCRs) recognize the same epitopes may not be exact TCR clonotypes but have slightly different sequences. However, changes in genomic and transcriptomic signatures of these highly homologous T cells during immunotherapy remain unknown. Here, we examined evolutionary features circulating observed tumors (tumor-infiltrating lymphocyte (TIL)-TCRs) by combining single-cell RNA/TCR sequencing longitudinal blood samples tumor tissue from a patient treated...
<p>Gating strategy to analyze CX3CR1 expression on CD8+ T cells in human melanoma TILs.</p>
<p>Single-cell profiling of melanoma-infiltrating cells from patients treated with immune checkpoint inhibitor therapy in the Sade-Feldman et al. data</p>
<p>The scheme of the generation Pmel-1 Cd2-cre/Cx3cr1DTR/DTR mice.</p>