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antonino bruno

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Papers by antonino bruno

Myeloid Derived Suppressor Cells Interactions With Natural Killer Cells and Pro-angiogenic Activities: Roles in Tumor Progression

Frontiers in Immunology, 2019

Myeloid-derived suppressor cells (MDSCs) contribute to the induction of an immune suppressive/ane... more Myeloid-derived suppressor cells (MDSCs) contribute to the induction of an immune suppressive/anergic, tumor permissive environment. MDSCs act as immunosuppression orchestrators also by interacting with several components of both innate and adaptive immunity. Natural killer (NK) cells are innate lymphoid cells functioning as primary effector of immunity, against tumors and virus-infected cells. Apart from the previously described anergy and hypo-functionality of NK cells in different tumors, NK cells in cancer patients show pro-angiogenic phenotype and functions, similar to decidual NK cells. We termed the pro-angiogenic NK cells in the tumor microenvironment "tumor infiltrating NK" (TINKs), and peripheral blood NK cells in cancer patients "tumor associated NK" (TANKs). The contribution of MDSCs in regulating NK cell functions in tumor-bearing host, still represent a poorly explored topic, and even less is known on NK cell regulation of MDSCs. Here, we review whether the crosstalk between MDSCs and NK cells can impact on tumor onset, angiogenesis and progression, focusing on key cellular and molecular interactions. We also propose that the similarity of the properties of tumor associated/tumor infiltrating NK and MDSC with those of decidual NK and decidual MDSCs during pregnancy could hint to a possible onco-fetal origin of these pro-angiogenic leukocytes.

Immunological Drivers in Graves' Disease: NK Cells as a Master Switcher

Frontiers in Endocrinology, 2020

Graves' disease (GD) is a common autoimmune cause of hyperthyroidism, which is eventually related... more Graves' disease (GD) is a common autoimmune cause of hyperthyroidism, which is eventually related to the generation of IgG antibodies stimulating the thyrotropin receptor. Clinical manifestations of the disease reflect hyperstimulation of the gland, causing thyrocyte hyperplasia (goiter) and excessive thyroid hormone synthesis (hyperthyroidism). The above clinical manifestations are preceded by still partially unraveled pathogenic actions governed by the induction of aberrant phenotype/functions of immune cells. In this review article we investigated the potential contribution of natural killer (NK) cells, based on literature analysis, to discuss the bidirectional interplay with thyroid hormones (TH) in GD progression. We analyzed cellular and molecular NK-cell associated mechanisms potentially impacting on GD, in a view of identification of the main NK-cell subset with highest immunoregulatory role.

Microbiota-Derived Natural Products Targeting Cancer Stem Cells: Inside the Gut Pharma Factory

International Journal of Molecular Sciences

Cancer stem cells (CSCs) have drawn much attention as important tumour-initiating cells that may ... more Cancer stem cells (CSCs) have drawn much attention as important tumour-initiating cells that may also be crucial for recurrence after chemotherapy. Although the activity of CSCs in various forms of cancer is complex and yet to be fully elucidated, opportunities for therapies targeting CSCs exist. CSCs are molecularly distinct from bulk tumour cells, so they can be targeted by exploiting their signature molecular pathways. Inhibiting stemness has the potential to reduce the risk posed by CSCs by limiting or eliminating their capacity for tumorigenesis, proliferation, metastasis, and recurrence. Here, we briefly described the role of CSCs in tumour biology, the mechanisms involved in CSC therapy resistance, and the role of the gut microbiota in cancer development and treatment, to then review and discuss the current advances in the discovery of microbiota-derived natural compounds targeting CSCs. Collectively, our overview suggests that dietary intervention, toward the production of t...

An Olive Oil Mill Wastewater Extract Improves Chemotherapeutic Activity Against Breast Cancer Cells While Protecting From Cardiotoxicity

Frontiers in Cardiovascular Medicine

Graphical The cartoon summarized the major approaches and insights of the manuscript: (A) the pos... more Graphical The cartoon summarized the major approaches and insights of the manuscript: (A) the possibility to recover waste material from extra-virgin olive oil (EVOO) processing that allows the repurposing of polyphenol-rich extracts characterized by (B) antiangiogenic activities in vivo, antiproliferative activities in vitro on BC cell lines (C), cardioprotective activities on rat and human cardiomyocytes (HCMs) (D), and in vivo on the zebrafish embryo heart (E).

Longevity-Associated Variant of BPIFB4 Confers Neuroprotection in the STHdh Cell Model of Huntington Disease

International Journal of Molecular Sciences, Dec 5, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more

Effect of a Purified Extract of Olive Mill Waste water on Endothelial Cell Proliferation, Apoptosis, Migration and Capillary-Like Structure in vitro and in vivo

Journal of Bioanalysis & Biomedicine, 2015

Olive oil, a major feature of the Mediterranean diet, is an important source of phenolic compound... more Olive oil, a major feature of the Mediterranean diet, is an important source of phenolic compounds. Poliphenols are associated with inhibition of several pathological processes, including cancer. Soluble phenolic compounds are contained in the aqueous part of olive and are discarded during oil production in the 'olive mill wastewaters'. Here we investigated the properties of a purified extract of olive mill wastewaters, named A009, as potential antiangiogenic compound. While the strong anti-oxidant activity of olive derived phenolic compounds has been well characterized, little is known about their anti-angiogenic properties. We investigated effects of A009 on endothelial cell morphogenesis, proliferation, migration and apoptosis, comparing the results obtained with the activity of a well-characterized olive oil phenol, Hydroxytyrosol (HT). Further, we tested the effects of A009 and HT in an in vivo angiogenesis assay. We found that A009 exerted strong anti-angiogenic effects both in vitro and in vivo, and that the complex natural purified extract has stronger anti-angiogenic potential when compared to the same concentrations of HT in most of the assays performed. These data demonstrate that a novel purified, polyphenol enriched extract with anti-angiogenic, and angiopreventive potential can be obtained from olive oil mill waste material, recovering useful products from an agricultural waste.

The NK cells phenotype and function in resected non small cell lung cancer: differences between squamous and adenocarcinoma

Adipose mesenchymal stem cell-derived soluble factors, produced under hypoxic condition, efficiently support in vivo angiogenesis

Cell Death Discovery

Tissue regeneration or healing both require efficient vascularization within a tissue-damaged are... more Tissue regeneration or healing both require efficient vascularization within a tissue-damaged area. Based on this concept, a remarkable number of strategies, aimed at developing new tools to support re-vascularization of damaged tissue have emerged. Among the strategies proposed, the use of pro-angiogenic soluble factors, as a cell-free tool, appears as a promising approach, able to overcome the issues concerning the direct use of cells for regenerative medicine therapy. Here, we compared the effectiveness of adipose mesenchymal stem cells (ASCs), use as cell suspension, ASC protein extract or ASC-conditioned-medium (i.e., soluble factors), combined with collagenic scaffold, in supporting in vivo angiogenesis. We also tested the capability of hypoxia in increasing the efficiency of ASC to promote angiogenesis, via soluble factors, both in vivo and in vitro. In vivo studies were performed using the Integra® Flowable Wound Matrix, and the Ultimatrix in sponge assay. Flow cytometry was...

The tumor innate immune microenvironment in prostate cancer: an overview of soluble factors and cellular effectors

Exploration of Targeted Anti-tumor Therapy

Prostate cancer (PCa) accounts as the most common non-cutaneous disease affecting males, and as t... more Prostate cancer (PCa) accounts as the most common non-cutaneous disease affecting males, and as the first cancer, for incidence, in male. With the introduction of the concept of immunoscore, PCa has been classified as a cold tumor, thus driving the attention in the development of strategies aimed at blocking the infiltration/activation of immunosuppressive cells, while favoring the infiltration/activation of anti-tumor immune cells. Even if immunotherapy has revolutionized the approaches to cancer therapy, there is still a window failure, due to the immune cell plasticity within PCa, that can acquire pro-tumor features, subsequent to the tumor microenvironment (TME) capability to polarize them. This review discussed selected relevant soluble factors [transforming growth factor-beta (TGFβ), interleukin-6 (IL-6), IL-10, IL-23] and cellular components of the innate immunity, as drivers of tumor progression, immunosuppression, and angiogenesis within the PCa-TME.

Results of a prospective observational study of autologous peripheral blood mononuclear cell therapy for no-option critical limb-threatening ischemia and severe diabetic foot ulcers

Cardiovascular Diabetology

Background Cell therapy with autologous peripheral blood mononuclear cells (PB-MNCs) may help res... more Background Cell therapy with autologous peripheral blood mononuclear cells (PB-MNCs) may help restore limb perfusion in patients with diabetes mellitus and critical limb-threatening ischemia (CLTI) deemed not eligible for revascularization procedures and consequently at risk for major amputation (no-option). Fundamental is to establish its clinical value and to identify candidates with a greater benefit over time. Assessing the frequency of PB circulating angiogenic cells and extracellular vesicles (EVs) may help in guiding candidate selection. Methods We conducted a prospective, non-controlled, observational study on no-option CLTI diabetic patients that underwent intramuscular PB-MNCs therapy, which consisted of more cell treatments repeated a maximum of three times. The primary endpoint was amputation rate at 1 year following the first treatment with PB-MNCs. We evaluated ulcer healing, walking capability, and mortality during the follow-up period. We assessed angiogenic cells an...

Human RNASET2: A Highly Pleiotropic and Evolutionary Conserved Tumor Suppressor Gene Involved in the Control of Ovarian Cancer Pathogenesis

International Journal of Molecular Sciences

Ovarian cancer represents one of the most malignant gynecological cancers worldwide, with an over... more Ovarian cancer represents one of the most malignant gynecological cancers worldwide, with an overall 5-year survival rate, being locked in the 25–30% range in the last decade. Cancer immunotherapy is currently one of the most intensively investigated and promising therapeutic strategy and as such, is expected to provide in the incoming years significant benefits for ovarian cancer treatment as well. Here, we provide a detailed survey on the highly pleiotropic oncosuppressive roles played by the human RNASET2 gene, whose protein product has been consistently reported to establish a functional crosstalk between ovarian cancer cells and key cellular effectors of the innate immune system (the monocyte/macrophages lineage), which is in turn able to promote the recruitment to the cancer tissue of M1-polarized, antitumoral macrophages. This feature, coupled with the ability of T2 ribonucleases to negatively affect several cancer-related parameters in a cell-autonomous manner on a wide rang...

Neutrophil and Natural Killer Cell Interactions in Cancers: Dangerous Liaisons Instructing Immunosuppression and Angiogenesis

Vaccines

The tumor immune microenvironment (TIME) has largely been reported to cooperate on tumor onset an... more The tumor immune microenvironment (TIME) has largely been reported to cooperate on tumor onset and progression, as a consequence of the phenotype/functional plasticity and adaptation capabilities of tumor-infiltrating and tumor-associated immune cells. Immune cells within the tumor micro (tissue-local) and macro (peripheral blood) environment closely interact by cell-to-cell contact and/or via soluble factors, also generating a tumor-permissive soil. These dangerous liaisons have been investigated for pillars of tumor immunology, such as tumor associated macrophages and T cell subsets. Here, we reviewed and discussed the contribution of selected innate immunity effector cells, namely neutrophils and natural killer cells, as “soloists” or by their “dangerous liaisons”, in favoring tumor progression by dissecting the cellular and molecular mechanisms involved.

Abstract 4044: An extract of olive oil wastewater enhances chemotherapy effects on breast cancer cells without exacerbating cardiovascular toxicity

Cancer Research

Background: In cancer patients receiving chemotherapeutic agents, cardiovascular toxicities still... more Background: In cancer patients receiving chemotherapeutic agents, cardiovascular toxicities still remains one of the most undesirable side effects. One of the best known cardiotoxic agents is doxorubicin, a very powerful chemotherapeutic molecules for breast cancer. Extra-virgin olive oil (EVOO) is rich in cancer preventive polyphenols endowed with anti-inflammatory, anti-oxidant activities which could exert protective effects on heart cells. A very interesting derivative of EVOO preparation is represented by purified extracts from olive mill waste waters (OMWW) rich in polyphenols. Here, we have investigated the anti-cancer activity of a OMWW preparation, named A009, on breast cancer cells when combined with chemotherapeutics, as well as its potential cardioprotective activities. We had previously reported additive effects with cisplatin in prostate cancer cells. In previous studies we have shown that the combination of A009 with cisplatin or 5-FU was effective in decreasing prosta...

In Vitro Evaluation of Antioxidant Potential of the Invasive Seagrass Halophila stipulacea

Marine Drugs

Marine organisms with fast growth rates and great biological adaptive capacity might have biotech... more Marine organisms with fast growth rates and great biological adaptive capacity might have biotechnological interests, since ecological competitiveness might rely on enhanced physiological or biochemical processes’ capability promoting protection, defense, or repair intracellular damages. The invasive seagrass Halophila stipulacea, a non-indigenous species widespread in the Mediterranean Sea, belongs to this category. This is the premise to investigate the biotechnological interest of this species. In this study, we investigated the antioxidant activity in vitro, both in scavenging reactive oxygen species and in repairing damages from oxidative stress on the fibroblast human cell line WI-38. Together with the biochemical analysis, the antioxidant activity was characterized by the study of the expression of oxidative stress gene in WI-38 cells in presence or absence of the H. stipulacea extract. Concomitantly, the pigment pool of the extracts, as well as their macromolecular compositi...

The Pharmacologist’s Point of View: Mechanisms of Cardiotoxicity

Manual of Cardio-oncology, 2017

Cancer chemotherapy has made remarkable advances in the treatment of both solid and hematologic m... more Cancer chemotherapy has made remarkable advances in the treatment of both solid and hematologic malignancies, and significant progress has been achieved in the reduction of recurrences. However, many anticancer agents, while successuful in their anti-tumor activities, are often associated with side effects affecting the cardiovascular compartment, leading to an increase in morbidity and mortality. Here we will discuss the cellular and molecular alterations occurring in the chemotherapy-induced cardiotoxicity, focusing on the main anti-cancer agent categories employed in cancer treatment and we report suggestions on screening approaches. We revise concept of cardio-oncology and cardio-oncological prevention, an interdisciplinary field that joins oncologists and cardiologists, with the necessary aim to limit or prevent chemotherapyinduced cardiotoxicity.

PKHhigh/CD133+/CD24− Renal Stem-Like Cells Isolated from Human Nephrospheres Exhibit In Vitro Multipotency

Cells, 2020

The mechanism upon which human kidneys undergo regeneration is debated, though different lineage-... more The mechanism upon which human kidneys undergo regeneration is debated, though different lineage-tracing mouse models have tried to explain the cellular types and the mechanisms involved. Different sources of human renal progenitors have been proposed, but it is difficult to argue whether these populations have the same capacities that have been described in mice. Using the nephrosphere (NS) model, we isolated the quiescent population of adult human renal stem-like PKHhigh/CD133+/CD24− cells (RSC). The aim of this study was to deepen the RSC in vitro multipotency capacity. RSC, not expressing endothelial markers, generated secondary nephrospheres containing CD31+/vWf+ cells and cytokeratin positive cells, indicating the coexistence of endothelial and epithelial commitment. RSC cultured on decellularized human renal scaffolds generated endothelial structures together with the proximal and distal tubular structures. CD31+ endothelial committed progenitors sorted from nephrospheres gen...

SARS-CoV-2 Immunization Orchestrates the Amplification of IFNγ-Producing T Cell and NK Cell Persistence

Frontiers in Immunology, 2022

A successful vaccination would represent the most efficient means to control the pandemic of Coro... more A successful vaccination would represent the most efficient means to control the pandemic of Coronavirus Disease-19 (COVID-19) that led to millions of deaths worldwide. Novel mRNA-based vaccines confer protective immunity against SARS-CoV-2, but whether immunity is immediately effective and how long it will remain in recipients are uncertain. We sought to assess the effectiveness of a two-dose regimen since the boosts are often delayed concerning the recommended intervals.MethodsA longitudinal cohort of healthcare workers (HCW, N = 46; 30.4% men; 69.6% women; mean age 36.05 ± 2.2 years) with no SARS-CoV-2 infection as documented by negative polymerase chain reaction was immunophenotyped in PBMC once a week for 4 weeks from the prime immunization (Pfizer mRNA BNT162b2) and had received 2 doses, to study the kinetic response.ResultsWe identified three risk groups to develop SARS-CoV-2 infection IgG+-based (late responders, R-; early responders, R+; pauci responders, PR). In all receip...

When a Friend Becomes Your Enemy: Natural Killer Cells in Atherosclerosis and Atherosclerosis-Associated Risk Factors

Frontiers in Immunology, 2022

Atherosclerosis (ATS), the change in structure and function of arteries with associated lesion fo... more Atherosclerosis (ATS), the change in structure and function of arteries with associated lesion formation and altered blood flow, is the leading cause of cardiovascular disease, the number one killer worldwide. Beyond dyslipidemia, chronic inflammation, together with aberrant phenotype and function of cells of both the innate and adaptive immune system, are now recognized as relevant contributors to atherosclerosis onset and progression. While the role of macrophages and T cells in atherosclerosis has been addressed in several studies, Natural Killer cells (NKs) represent a poorly explored immune cell type, that deserves attention, due to NKs’ emerging contribution to vascular homeostasis. Furthermore, the possibility to re-polarize the immune system has emerged as a relevant tool to design new therapies, with some succesfull exmples in the field of cancer immunotherapy. Thus, a deeper knowledge of NK cell pathophysiology in the context of atherosclerosis and atherosclerosis-associat...

A polyphenol-rich extract of Olive Mill Wastewater Enhances cancer chemotherapy effects, while mitigating cardiac toxicity

BackgroundCardiovascular toxicities still remain one of the most undesirable side effects in canc... more BackgroundCardiovascular toxicities still remain one of the most undesirable side effects in cancer patients receiving chemotherapy, and cardiotoxicity has been detected associated with many therapeutic regimens. A number of mechanisms are reported for these effects, some of which are related to inflammation, oxygen radical generation, mitochondrial damage. Extra-virgin olive oil (EVOO) is rich in cancer preventive polyphenols endowed with anti-inflammatory, antioxidant activities which could exert protective effects on the heart cells. One very interesting derivative of EVOO preparation is represented by purified extract form waste waters. Here, we investigated the anti-cancer activity when combined with chemotherapeutics as well as potential cardioprotective activities of a polyphenol-rich extract from waste product of the EVOO, named A009.Methods and ResultsMice bearing prostate cancer (PCa) xenografts were treated with cisplatin with and without A009. Tumor cell growth was reduc...

The pro-angiogenic phenotype and functions of colorectal cancer tumour infiltrating (TINKs) and tumour associated (TANKs) natural killer cells