A5062396581- Immune Cell Function and Interaction
- Chemokine receptors and signaling
- Immune cells in cancer
- Immunotherapy and Immune Responses
- Signaling Pathways in Disease
- Multiple Myeloma Research and Treatments
- RNA Interference and Gene Delivery
- Histone Deacetylase Inhibitors Research
- Endoplasmic Reticulum Stress and Disease
- Heat shock proteins research
- Cancer Immunotherapy and Biomarkers
- ATP Synthase and ATPases Research
- interferon and immune responses
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Inflammation biomarkers and pathways
- Cell Adhesion Molecules Research
- Nanoparticle-Based Drug Delivery
- T-cell and B-cell Immunology
- S100 Proteins and Annexins
- Immune Response and Inflammation
- Tissue Engineering and Regenerative Medicine
- Epigenetics and DNA Methylation
- Ferroptosis and cancer prognosis
- Extracellular vesicles in disease
AstraZeneca (United States)
2022-2024
AstraZeneca (Japan)
2024
The Wistar Institute
2019-2023
Sapienza University of Rome
2015-2017
Istituto Pasteur
2015
In this study, using single-cell RNA-seq, cell mass spectrometry, flow cytometry, and functional analysis, we characterized the heterogeneity of polymorphonuclear neutrophils (PMNs) in cancer. We describe three populations PMNs tumor-bearing mice: classical PMNs, myeloid-derived suppressor cells (PMN-MDSCs), activated PMN-MDSCs with potent immune suppressive activity. spleens mice, gradually replaced during tumor progression. Activated were found only tumors, where they present at very early...
Abstract Natural killer (NK) cells are key innate immune effectors against multiple myeloma, their activity declining in myeloma patients with disease progression. To identify the mechanisms underlying NK cell functional impairment, we characterized distribution of functionally distinct subsets bone marrow myeloma-bearing mice. Herein report that number KLRG1− endowed potent effector function rapidly and selectively decreases during growth, this correlating decreased degranulation vivo....
Abstract Myeloid-derived suppressor cells (MDSC) are pathologically activated neutrophils and monocytes with potent immune suppressive activity. These play an important role in accelerating tumor progression undermining the efficacy of anti-cancer therapies. The natural mechanisms limiting MDSC activity not well understood. Here, we present evidence that type I interferons (IFN1) receptor signaling serves as a universal mechanism restricts acquisition by these cells. Downregulation IFNAR1...
Abstract Purpose: To evaluate the mechanisms of how therapeutic upregulation transcription factor, CCAAT/enhancer-binding protein alpha (C/EBPα), prevents tumor progression in patients with advanced hepatocellular carcinoma (HCC) and different mouse models. Experimental Design: We conducted a phase I trial 36 HCC (NCT02716012) who received sorafenib as part their standard care, were given C/EBPα small activating RNA (saRNA; MTL-CEBPA) either neoadjuvant or adjuvant treatment. In preclinical...
Abstract The Ataxia telangiectasia and Rad3-related (ATR) inhibitor ceralasertib in combination with the PD-L1 antibody durvalumab demonstrated encouraging clinical benefit melanoma lung cancer patients who progressed on immunotherapy. Here we show that modelling of intermittent treatment mouse tumor models reveals CD8 + T-cell dependent antitumor activity, which is separate from effects cells. Ceralasertib suppresses proliferating T-cells rapidly reversed off-treatment. causes up-regulation...
Abstract Several immune cell populations are involved in cartilage damage, bone erosion, and resorption processes during osteoarthritis. The purpose of this study was to investigate the role NK cells pathogenesis experimental osteoarthritis whether how neutrophils can regulate their synovial localization disease. Experimental elicited by intra-articular injection collagenase wild type Cxcr3−/− 8-wk old mice. To follow progression, thickening, osteophyte formation were measured...
Antibodies targeting CTLA-4 induce durable responses in some patients with melanoma and are being tested a variety of human cancers. However, these therapies ineffective for majority across tumor types. Further understanding the immune alterations induced by may enable development novel strategies to enhance control biomarkers identify most likely respond. In several murine models, including colon26, MC38, CT26, B16 tumors cotreated GVAX, anti-CTLA-4 efficacy depends on interactions between...
Metastatic dissemination remains a significant barrier to successful therapy for melanoma. Wnt5A is potent driver of invasion in melanoma and believed be secreted from the tumor microenvironment (TME). Our data suggest that myeloid-derived suppressor cells (MDSC) TME are major source reliant upon multiple actions. Knockdown specifically myeloid demonstrated clear decrease expression within
The protein chaperone HSP70 is overexpressed in many cancers including colorectal cancer, where overexpression associated with poor survival. We report here the creation of a uniquely acting inhibitor (HSP70i) that targets multiple compartments cancer cell, mitochondria. This was mitochondria toxic and cytotoxic to cells, but not normal colon epithelial cells. Inhibition efficacious as single agent primary metastatic models enabled identification novel mitochondrial client proteins for...
Abstract Pathologically activated neutrophils (PMN) with immunosuppressive activity, which are termed myeloid-derived suppressor cells (PMN-MDSC), play a critical role in regulating tumor progression. These have been implicated promoting metastases by contributing to premetastatic niche formation. This effect was facilitated enhanced spontaneous migration of PMN from bone marrow the niches during early-stage cancer development. The molecular mechanisms underpinning this phenomenon remained...
<div>AbstractPurpose:<p>To evaluate the mechanisms of how therapeutic upregulation transcription factor, CCAAT/enhancer-binding protein alpha (C/EBPα), prevents tumor progression in patients with advanced hepatocellular carcinoma (HCC) and different mouse models.</p>Experimental Design:<p>We conducted a phase I trial 36 HCC (NCT02716012) who received sorafenib as part their standard care, were given C/EBPα small activating RNA (saRNA; MTL-CEBPA) either neoadjuvant or...
<p>Supplementary Figure 1, Supplementary 2, 3, 4, 5, 6, 7</p>
Abstract This study is aimed to investigate the effect of ATR inhibitor (ATRi) ceralasertib on tumor microenvironment (TME). Ceralasertib has demonstrated encouraging clinical benefits in patients with non-small cell lung cancer who were resistant PD1/PDL1 treatment. Using different pre-clinical mouse models, we found that antitumor was dependent CD8 T cells. In fact, depletion cells abrogated therapeutic ATRi. treatment caused pleotropic TME. It improved function cells, depleted associated...
Abstract Medulloblastoma (MB) is the most common paediatric neoplasm of CNS. Standard therapy mainly curative; however, severe side effects make immunotherapy an attractive therapeutic option. Natural Killer (NK) cells are innate lymphoid that can be used for adoptive cell therapy. Herein, we studied role NK in MB growth control, focusing on Sonic Hedgehog (SHH) subgroup, using line DAOY. The contribution SHH pathway recruitment to was analysed performing orthotopic xenograft DAOY nude mice...
<div>Abstract<p>Natural killer (NK) cells are key innate immune effectors against multiple myeloma, their activity declining in myeloma patients with disease progression. To identify the mechanisms underlying NK cell functional impairment, we characterized distribution of functionally distinct subsets bone marrow myeloma-bearing mice. Herein report that number KLRG1<sup>−</sup> endowed potent effector function rapidly and selectively decreases during growth, this...
<div>Abstract<p>Metastatic dissemination remains a significant barrier to successful therapy for melanoma. Wnt5A is potent driver of invasion in melanoma and believed be secreted from the tumor microenvironment (TME). Our data suggest that myeloid-derived suppressor cells (MDSC) TME are major source reliant upon multiple actions. Knockdown specifically myeloid demonstrated clear decrease expression within <i>in vivo</i> as well intratumoral MDSC regulatory T cell...
<div>Abstract<p>The protein chaperone HSP70 is overexpressed in many cancers including colorectal cancer, where overexpression associated with poor survival. We report here the creation of a uniquely acting inhibitor (HSP70i) that targets multiple compartments cancer cell, mitochondria. This was mitochondria toxic and cytotoxic to cells, but not normal colon epithelial cells. Inhibition efficacious as single agent primary metastatic models enabled identification novel...