A5049488255- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Melanoma and MAPK Pathways
- Nanoplatforms for cancer theranostics
- Cutaneous Melanoma Detection and Management
- Ovarian cancer diagnosis and treatment
- Nanoparticle-Based Drug Delivery
- Cancer Genomics and Diagnostics
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Lung Cancer Research Studies
- Immunodeficiency and Autoimmune Disorders
- Ocular Oncology and Treatments
- interferon and immune responses
- Angiogenesis and VEGF in Cancer
- Chronic Lymphocytic Leukemia Research
- Peptidase Inhibition and Analysis
- Single-cell and spatial transcriptomics
- Cell death mechanisms and regulation
- Virus-based gene therapy research
- Invertebrate Immune Response Mechanisms
- Aquaculture disease management and microbiota
- Ubiquitin and proteasome pathways
Mayo Clinic in Arizona
2015-2024
Mayo Clinic
2017-2024
WinnMed
2019-2024
Mayo Clinic in Florida
2019-2024
Nemours Children’s Clinic
2023
Jacksonville College
2019-2023
Huazhong Agricultural University
2020-2023
GTx (United States)
2020
Qingdao National Laboratory for Marine Science and Technology
2020
York General Hospital
2013-2014
Although immune checkpoint inhibitors have resulted in durable clinical benefits a subset of patients with advanced cancer, some who did not respond to initial anti-PD-1 therapy been found benefit from the addition salvage chemotherapy. However, mechanism responsible for successful chemoimmunotherapy is completely understood. Here we show that circulating CD8+ T cells expressing chemokine receptor CX3CR1 are able withstand toxicity chemotherapy and increased metastatic melanoma responded...
Both targeted therapies and immunotherapies provide benefit in resected Stage III melanoma. We hypothesized that the combination of immunotherapy given prior to therapeutic lymph node dissection (TLND) would be tolerable drive robust pathologic responses. In NeoACTIVATE (NCT03554083), a Phase II trial, patients with clinically evident resectable melanoma received either 12 weeks neoadjuvant vemurafenib, cobimetinib, atezolizumab (BRAF-mutated, Cohort A, n = 15), or cobimetinib...
Abstract Cytotoxic CD8+ T cells (CTL) are a crucial component of the immune system notable for their ability to eliminate rapidly proliferating malignant cells. However, T-cell intrinsic factors required human CTLs accomplish highly efficient antitumor cytotoxicity not well defined. By evaluating from responders versus nonresponders treatment with checkpoint inhibitors, we sought identify key associated effective CTL function. Single-cell RNA-sequencing analysis peripheral patients treated...
Management of PD-1 blockade resistance in metastatic melanoma (MM) remains challenging. Immunotherapy or chemotherapy alone provides limited benefit this setting. Chemo-immunotherapy (CIT) has demonstrated favorable efficacy and safety profiles lung cancer. Our pre-clinical study showed that MM patients who have failed blockade, the addition increases CX3CR1+ therapy-responsive CD8+ T-cells with enhanced anti-tumor activity, resulting improved clinical response. Here, we examined outcomes...
Background Trans-acting programmed death-ligand 1 (PD-L1) derives from malignant cells in three known forms. High levels of secreted splice variant PD-L1 (sPD-L1), ADAM10/ADAM17-shed sPD-L1, and PD-L1-positive extracellular vesicles (evPD-L1) each predict poor prognosis limited response to PD-(L)1 checkpoint inhibitors cancer. To our knowledge, no clinical intervention has reduced any these circulating forms PD-L1. Here, we explore therapeutic plasma exchange (TPE) as a treatment reduce...
AB160 is a 160-nm nano-immunoconjugate consisting of nab-paclitaxel (ABX) nanoparticles noncovalently coated with bevacizumab (BEV) for targeted delivery into tissues expressing high levels VEGF. Preclinical data showed that resulted in greater tumor targeting and inhibition compared sequential treatment ABX then BEV. Given individual drug activity, we investigated the safety toxicity patients gynecologic cancers.
Development of resistance to chemotherapy is a major obstacle in extending the survival patients with cancer. Although originally defined as an immune checkpoint molecule, B7-H1 (also named PD-L1 or CD274) was found play role cancer chemoresistance; however, underlying mechanism action regulation sensitivity remains unclear cells. Here we show that development chemoresistance depends on increased activation ERK cells overexpressing B7-H1. Conversely, knockout (KO) by CRISPR/Cas9 renders...
The peripheral blood lymphocyte-to-monocyte ratio (LMR) has been associated with prognosis in many malignancies including metastatic melanoma. However, it not studied patients treated immune checkpoint inhibitors. In this study, we analyzed the baseline LMR progression-free survival (PFS) and overall (OS) melanoma pembrolizumab. A total of 133 pembrolizumab were included retrospective study. was calculated from pretherapy counts optimal cutoff value determined by a receiver operator...
With the continuous innovation of modern technology, Internet has integrated into every corner society. For middle school students, how to leverage advantages while avoiding excessive addiction it become a hot topic social discussion at this stage. In information age, people are accustomed obtaining various through Internet, which is convenient operate, fast and wide in transmission, but also exposes many negative issues. Especially, young students excessively addicted makes their studies...
CpG oligodeoxynucleotides, as a ligand of toll-like receptor (TLR)-9, have demonstrated promising antitumor effects in some clinical trials; however, its toxicity and low efficacy systemic therapy has limited therapeutic applications. In order to improve efficacy, we investigated the mechanisms CpG-induced immunity context CD8+ T cell responses. We show that IL-12 is required for expansion IFN-γ producing tumor-reactive cells capable rejecting tumors. addition, CpGs reduced PD-1 expression...
Introduction Metastatic uveal melanoma (MUM) has a poor prognosis and treatment options are limited. These patients do not typically experience durable responses to immune checkpoint inhibitors (ICIs). Oncolytic viruses (OV) represent novel approach immunotherapy for with MUM. Methods We developed an OV Vesicular Stomatitis Virus (VSV) vector modified express interferon-beta (IFN-β) Tyrosinase Related Protein 1 (TYRP1) (VSV-IFNβ-TYRP1), conducted Phase clinical trial 3 + design in...
Artemis, a member of the SNM1 gene family, is multifunctional phospho-protein that has been shown to have important roles in V(D)J recombination, DNA double strand break repair, and stress-induced cell-cycle checkpoint regulation. We show here Artemis interacts with Cul4A-DDB1 E3 ubiquitin ligase via direct interaction substrate-specificity receptor DDB2. Furthermore, also CDK inhibitor tumor suppressor p27, substrate ligase, both DDB2 are required for degradation p27 mediated by this...
We report here a patient with stage IV mucosal melanoma treated dual immune checkpoint inhibitor (ICI) therapy (Nivolumab/Ipilimumab) who experienced rapid disease progression and metastatic spread within three weeks of first infusion. Surprisingly, this also developed fulminant myocarditis the same time frame. Immunohistochemical staining primary tumor omental lesion revealed robust CD8+ PD-1+ T cell infiltration after ICI treatment, as would be expected following activation. However,...
Abstract Seven different anti–PD-1 and PD-L1 mAbs are now widely used in the United States to treat a variety of cancer types, but no clinical trials have compared them directly. Furthermore, because many these Abs do not cross-react between mouse human proteins, preclinical models exist which consider types questions. Thus, we produced humanized PD-1 mice extracellular domains both were replaced with corresponding sequences. Using this new model, sought compare strength immune response...
Background Patients with regionally advanced melanoma are at high risk of distant failure and unlikely to be cured by surgery alone. Neoadjuvant therapy may provide benefit in these patients. Objectives To evaluate our experience neoadjuvant systemic high‐risk stage III Methods Retrospective review patients disease who received between August 2009 2016 Mayo Clinic Rochester. Results Twenty‐three cases met inclusion criteria, 16 resectable 7 unresectable disease. No one patient borderline...
Herpesviral hematopoietic necrosis disease caused by cyprinid herpesvirus 2 (CyHV-2) results in huge economic losses for the gibel carp (Carassius auratus gibelio) aquaculture industry. A vaccination strategy is a feasible method to prevent CyHV-2 infection and resulting losses. In this study, inactivators (including β-propiolactone, formaldehyde binary ethylenimine) were used prepare an inactivated vaccine. The optimal vaccine (0.2% β-propiolactone inactivates 48 h) mixed with β-glucan,...
Patients with advanced cancers who either do not experience initial response to or progress while on immune checkpoint inhibitors (ICIs) receive salvage radiotherapy reduce tumor burden and tumor-related symptoms. Occasionally, some patients substantial global regression a rebound of cytotoxic CD8
e23269 Background: Most cases of malignant melanoma are cutaneous, with ≈50% having a BRAF driver mutation that predicts response to MAPK pathway inhibitors. A small minority harbor an activating KIT mutation, most notably in mucosal and acral melanomas (15-20%) occasionally those arising from chronic sun-damaged skin (2-3%). Only about third mutated respond targeted therapy Imatinib, yet data is scarce limited, especially older patients. We sought characterize the efficacy toxicity Imatinib...
Direct interactions between tumor and immune cells mediate the antitumor effect of all modern cancer immunotherapeutic agents. Simultaneously, have evolved mechanisms evasion including downregulation HLA-I potentially disrupting mechanism action employed by many checkpoint inhibitors. And yet in situ interplay these within microenvironment (TIME) remains elusive. Recent advances histologic multiplex bioimaging platforms enabled in-depth molecular characterization single spatially-preserved...
Large granular lymphocyte (LGL) leukemia is a chronic clonal lymphoproliferative disorder. Here, T-LGL patient developed NK-LGL with residual leukemic T-LGL. TCRVβ usage and CDR3 sequence drifts were observed disease progression. A STAT3 S614R mutation was identified in NK but not T-cells the mixed stage. Multiple, non-dominant T-cell clones distinct mutations present throughout. Our results suggest that T may share common pathogenesis mechanisms alone insufficient to bring about expansion....