A5071381547- Immune Cell Function and Interaction
- Immune cells in cancer
- Extracellular vesicles in disease
- T-cell and B-cell Immunology
- Epigenetics and DNA Methylation
- Immunotherapy and Immune Responses
- Cytomegalovirus and herpesvirus research
- Telomeres, Telomerase, and Senescence
- Bone health and treatments
- Muscle Physiology and Disorders
- Wnt/β-catenin signaling in development and cancer
- Mitochondrial Function and Pathology
- Immune Response and Inflammation
- Cell Adhesion Molecules Research
- Prostate Cancer Treatment and Research
- Cancer Cells and Metastasis
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Radiopharmaceutical Chemistry and Applications
- Melanoma and MAPK Pathways
- Biomarkers in Disease Mechanisms
- Cytokine Signaling Pathways and Interactions
- Inflammasome and immune disorders
- Fibroblast Growth Factor Research
- Cancer Immunotherapy and Biomarkers
Washington University in St. Louis
2016-2025
Bambino Gesù Children's Hospital
2021-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2021-2024
Sapienza University of Rome
2013-2017
Istituto Pasteur
2013-2016
University of Siena
2014
University of Florence
2014
Instituto Pasteur
2013
Tumor–stroma interactions contribute to tumorigenesis. Tumor cells can educate the stroma at primary and distant sites facilitate recruitment of heterogeneous populations immature myeloid cells, known as myeloid-derived suppressor (MDSCs). MDSCs suppress T cell responses promote tumor proliferation. One outstanding question is how local modulate during progression. Down-regulation β-catenin critical for MDSC accumulation immune suppressive functions in mice humans. Here, we demonstrate that...
Abstract Chemotherapy is important for cancer treatment, however, toxicities limit its use. While great strides have been made to ameliorate the acute induced by chemotherapy, long-term comorbidities including bone loss remain a significant problem. Chemotherapy-driven estrogen postulated drive loss, but data suggests existence of an estrogen-independent mechanism loss. Using clinically relevant mouse models, we showed that senescence and senescence-associated secretory phenotype (SASP)...
Increasing evidence indicates that cancer cell stress induced by chemotherapeutic agents promote antitumor immune responses and contribute to their full clinical efficacy. In this article, we identify the signaling events underlying chemotherapy-induced NKG2D DNAM-1 ligand expression on multiple myeloma (MM) cells. Our findings indicate sublethal doses of doxorubicin melphalan initiate a DNA damage response (DDR) controlling upregulation MM lines patient-derived malignant plasma cells in...
Abstract The NLRP3 inflammasome senses a variety of signals referred to as danger associated molecular patterns (DAMPs), including those triggered by crystalline particulates or degradation products extracellular matrix. Since some DAMPs confer tissue-specific activation the inflammasomes, we tested hypothesis that bone matrix components function for and regulate osteoclast differentiation. Indeed, particles cause exuberant osteoclastogenesis in presence RANKL, response correlates with...
Abstract Treatment of multiple myeloma (MM) cells with sublethal doses genotoxic drugs leads to senescence and results in increased NK cell recognition effector functions. Herein, we demonstrated that doxorubicin- melphalan-treated senescent display expression IL15, a cytokine involved activation, proliferation, maturation. IL15 upregulation was evident at the mRNA protein level, both MM lines malignant plasma from patients’ bone marrow (BM) aspirates. However, detectable as soluble only...
Toll-like receptors (TLRs) are pattern-recognition sensors mainly expressed in innate immune cells that directly recognize conserved pathogen structures (pathogen-associated molecular patterns-PAMPs). Natural killer (NK) have been described to express different endosomal TLRs triggered by RNA and DNA sequences derived from both viruses bacteria. This study was addressed establish which TLR could mediate NK activation function after proper stimuli. It also important the most suitable agonist...
In early infected or severe coronavirus disease 2019 (COVID-19) patients, circulating NK cells are consistently reduced, despite being highly activated exhausted. The aim of this paper was to establish whether acute respiratory syndrome 2 (SARS-CoV-2) spike glycoprotein (SP) may directly trigger and through which receptor(s).
DNAX accessory molecule-1 (DNAM-1) is an activating receptor constitutively expressed by macrophages/dendritic cells and T lymphocytes Natural Killer (NK) cells, having important role in anticancer responses; this regard, combination therapies able to enhance the expression of DNAM-1 ligands on tumor are therapeutic interest. In study, we investigated effect different nitric oxide (NO) donors ligand Poliovirus Receptor/CD155 (PVR/CD155) multiple myeloma (MM) cells. Six MM cell lines,...
We designed 39 new 2-phenylindole derivatives as potential anticancer agents bearing the 3,4,5-trimethoxyphenyl moiety with a sulfur, ketone, or methylene bridging group at position 3 of indole and halogen methoxy substituent(s) positions 4-7. Compounds 33 44 strongly inhibited growth P-glycoprotein-overexpressing multi-drug-resistant cell lines NCI/ADR-RES Messa/Dx5. At 10 nM, stimulated cytotoxic activity NK cells. 20-50 arrested >80% HeLa cells in G2/M phase cycle, stable arrest mitotic...
Recognition of tumor cells by the immune system is a key step in cancer eradication. Melphalan an alkylating agent routinely used treatment patients with multiple myeloma (MM), but at therapeutic doses it leads to immunosuppressive state due lymphopenia. Here, we mouse model MM investigate ability vivo low melphalan modulate natural killer (NK) cell activity, which have been shown play major role control growth. was able enhance surface expression stress-induced NKG2D ligands RAE-1 and...
Malignant cells constitutively express Natural killer group 2, member D (NKG2D) or DNAX Accessory Molecule-1 (DNAM-1) ligands, yet they are often unable to trigger a robust cytotoxic cell response. It may be therapeutically useful implement strategies aimed at increasing the density of NKG2D and DNAM-1 ligands on surface cancer cells, endowing them with capacity activate potent antitumor natural killer-cell responses.
The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful replication and preventing stress also emerging. Inactivation the MRN invariably leads to developmental and/or degenerative neuronal defects, pathogenesis which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly strongly impaired cerebellar development, both humans mouse model. These phenotypes strikingly overlap those induced...
Abstract Mechanisms related to tumor evasion from NK cell-mediated immune surveillance remain enigmatic. Dickkopf-1 (DKK1) is a Wnt/β-catenin inhibitor, whose levels correlate with breast cancer progression. We find DKK1 be expressed by cells and cancer-associated fibroblasts (CAFs) in patient samples orthotopic tumors, bone. By using genetic approaches, we that bone-derived contributes the systemic elevation tumor-bearing female mice, while CAFs contribute at primary site. Systemic...
The mechanisms that regulate the expression of NKG2D and DNAM-1 activating ligands are only partially known, but it is now widely established their finely regulated at transcriptional, post-transcriptional post-translational level, involve numerous stress pathways depending on type ligand, stressor, cell context.We show treatment Multiple Myeloma (MM) cells with sub-lethal doses Vincristine (VCR), an anticancer drug inhibits assembly microtubules, stimulates ligands, rendering these more...
In studies carried out previously, we demonstrated that small ubiquitin-like modifier 1 (SUMO1) is associated with poor sperm motility when evaluated a protocol reveals mostly SUMO1-ylated live sperm. Recently, another protocol, it has been SUMO expressed in most and related to morphology motility, suggesting sumoylation may have multiple roles depending on its localisation targets. We show herein, by confocal microscopy co-immunoprecipitation, dynamin-related protein (DRP1), Ran...
Cancer-associated fibroblasts (CAFs) are a heterogeneous population of mesenchymal cells supporting tumor progression, whose origin remains to be fully elucidated. Osterix (Osx) is marker osteogenic differentiation, expressed in skeletal progenitor stem and bone-forming osteoblasts. We report Osx expression CAFs by using Osx-cre;TdTomato reporter mice we confirm the presence pro-tumorigenic function TdT OSX + extra-skeletal tumors. Surprisingly, only minority expresses fibroblast markers....
Abstract Overwhelming evidence indicates that excessive stimulation of innate immune receptors the NOD‐like receptor (NLR) family causes significant damage to multiple tissues, yet role these proteins in bone metabolism is not well known. Here, we studied interaction between NLRP3 and NLRC4 inflammasomes homeostasis disease. We found loss or inflammasome attenuated osteoclast differentiation vitro. At tissue level, lack NLRP3, a lesser extent, resulted higher baseline mass compared wild‐type...
Several lines of evidence show that de novo expression carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is strongly associated with reduced disease-free survival patients affected by metastatic melanoma. Previously published investigations report homophilic interactions between CEACAM1 expressed on natural killer (NK) cells and tumors inhibit the NK cell-mediated killing independently major histocompatibility complex class I recognition. This biological property can be...
MDSCs comprise a heterogeneous population of immature Gr1 + /CD11b cells in mice and CD33 humans (Gabrilovich et al., 2012).This myeloid is further classified into granulocytic or monocytic based on the expression levels Ly6G Ly6C, respectively, mouse model CD15 CD14 humans.Investigations mechanisms that drive MDSC recruitment activity have shown GM-CSF, IL-6, VEGF play an important role via modulation Jak-STAT signaling pathways 2001;Trikha Carson, 2014).In addition to Jak-STAT, we recently...
The inhibitory receptor interleukin-1 8 (IL-1R8) has been recently recognized to be expressed also by human natural killer (NK) cells. This study was aimed design and optimize IL-1R8 silencing conditions in NK cells precisely establish the activity of such these Electroporation freshly isolated or IL-2-cultured with small interfering RNA (siRNA), resulted a marked, even though variable, IL-1R8-silencing. Although expression profile revealed downregulation most genes involved several...