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Article: Cigarette Smoking as a Risk Factor for Tuberculosis in Adults: Epidemiology and Aspects of Disease Pathogenesis.

Feldman, Charles / Theron, Annette J / Cholo, Moloko C / Anderson, Ronald

2024 Volume 13, Issue 2

Abstract: It has been noted by the World Health Organisation that cases of tuberculosis in 2022 globally numbered 10.6 million, resulting in 1.3 million deaths, such that TB is one of the infectious diseases causing the greatest morbidity and mortality worldwide. ... ...

Abstract	It has been noted by the World Health Organisation that cases of tuberculosis in 2022 globally numbered 10.6 million, resulting in 1.3 million deaths, such that TB is one of the infectious diseases causing the greatest morbidity and mortality worldwide. Since as early as 1918, there has been an ongoing debate as to the relationship between cigarette smoking and TB. However, numerous epidemiological studies, as well as meta-analyses, have indicated that both active and passive smoking are independent risk factors for TB infection, development of reactivation TB, progression of primary TB, increased severity of cavitary disease, and death from TB, among several other considerations. With this considerable body of evidence confirming the association between smoking and TB, it is not surprising that TB control programmes represent a key potential preventative intervention. In addition to coverage of the epidemiology of TB and its compelling causative link with smoking, the current review is also focused on evidence derived from clinical- and laboratory-based studies of disease pathogenesis, most prominently the protective anti-mycobacterial mechanisms of the alveolar macrophage, the primary intracellular refuge of
Language	English
Publishing date	2024-02-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens13020151
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Article ; Online: Pro-Tumorigenic and Thrombotic Activities of Platelets in Lung Cancer.

Anderson, Ronald / Rapoport, Bernardo L / Steel, Helen C / Theron, Annette J

International journal of molecular sciences

2023 Volume 24, Issue 15

Abstract: Aside from their key protective roles in hemostasis and innate immunity, platelets are now recognized as having multifaceted, adverse roles in the pathogenesis, progression and outcome of many types of human malignancy. The most consistent and compelling ...

Abstract	Aside from their key protective roles in hemostasis and innate immunity, platelets are now recognized as having multifaceted, adverse roles in the pathogenesis, progression and outcome of many types of human malignancy. The most consistent and compelling evidence in this context has been derived from the notable association of elevated circulating platelet counts with the onset and prognosis of various human malignancies, particularly lung cancer, which represents the primary focus of the current review. Key topics include an overview of the association of lung cancer with the circulating platelet count, as well as the mechanisms of platelet-mediated, pro-tumorigenic immunosuppression, particularly the role of transforming growth factor beta 1. These issues are followed by a discussion regarding the pro-tumorigenic role of platelet-derived microparticles (PMPs), the most abundant type of microparticles (MPs) in human blood. In this context, the presence of increased levels of PMPs in the blood of lung cancer patients has been associated with tumor growth, invasion, angiogenesis and metastasis, which correlate with disease progression and decreased survival times. The final section of the review addresses, firstly, the role of cancer-related platelet activation and thrombosis in the pathogenesis of secondary cardiovascular disorders and the associated mortality, particularly in lung cancer, which is second only to disease progression; secondly, the review addresses the potential role of antiplatelet agents in the adjunctive therapy of cancer.
MeSH term(s)	Humans ; Blood Platelets/metabolism ; Cell-Derived Microparticles/metabolism ; Thrombosis/metabolism ; Lung Neoplasms/metabolism ; Carcinogenesis/metabolism ; Disease Progression
Language	English
Publishing date	2023-07-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241511927
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Article ; Online: Immunopathogenesis of Immune Checkpoint Inhibitor-Related Adverse Events: Roles of the Intestinal Microbiome and Th17 Cells.

Anderson, Ronald / Theron, Annette J / Rapoport, Bernardo L

Frontiers in immunology

2019 Volume 10, Page(s) 2254

Abstract: The advent of novel, innovative, and effective anti-cancer immunotherapies has engendered an era of renewed optimism among cancer specialists and their patients. Foremost among these successful immunotherapies are monoclonal antibodies (MAbs) which ... ...

Abstract	The advent of novel, innovative, and effective anti-cancer immunotherapies has engendered an era of renewed optimism among cancer specialists and their patients. Foremost among these successful immunotherapies are monoclonal antibodies (MAbs) which target immune checkpoint inhibitor (ICI) molecules, most prominently cytotoxic T-lymphocyte-associated protein (CTLA-4) and programmed cell death protein-1 (PD-1) and its major ligand, PD-L1. These immunotherapeutic agents are, however, often associated with the occurrence of immune-mediated toxicities known as immune-related adverse events (IRAEs). The incidence of severe toxicities increases substantially when these agents are used together, particularly with CTLA-4 in combination with PD-1 or PD-L1 antagonists. Accordingly, dissociating the beneficial anti-tumor therapeutic activity of these agents from the emergence of IRAEs represents a significant challenge to attaining the optimum efficacy of ICI-targeted immunotherapy of cancer. This situation is compounded by an increasing awareness, possibly unsurprising, that both the beneficial and harmful effects of ICI-targeted therapies appear to result from an over-reactive immune system. Nevertheless, this challenge may not be insurmountable. This contention is based on acquisition of recent insights into the role of the gut microbiome and its products as determinants of the efficacy of ICI-targeted immunotherapy, as well as an increasing realization of the enigmatic involvement of Th17 cells in both anti-tumor activity and the pathogenesis of some types of IRAEs. Evidence linking the beneficial and harmful activities of ICI-targeted immunotherapy, recent mechanistic insights focusing on the gut microbiome and Th17 cells, as well as strategies to attenuate IRAEs in the setting of retention of therapeutic activity, therefore represent the major thrusts of this review.
MeSH term(s)	Antineoplastic Agents, Immunological/adverse effects ; Antineoplastic Agents, Immunological/therapeutic use ; B7-H1 Antigen/antagonists & inhibitors ; B7-H1 Antigen/immunology ; B7-H1 Antigen/metabolism ; CTLA-4 Antigen/antagonists & inhibitors ; CTLA-4 Antigen/immunology ; CTLA-4 Antigen/metabolism ; Gastrointestinal Microbiome/drug effects ; Gastrointestinal Microbiome/immunology ; Humans ; Immunotherapy/adverse effects ; Immunotherapy/methods ; Ipilimumab/adverse effects ; Ipilimumab/therapeutic use ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms/therapy ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Programmed Cell Death 1 Receptor/immunology ; Programmed Cell Death 1 Receptor/metabolism ; Th17 Cells/drug effects ; Th17 Cells/immunology ; Th17 Cells/metabolism
Chemical Substances	Antineoplastic Agents, Immunological ; B7-H1 Antigen ; CD274 protein, human ; CTLA-4 Antigen ; CTLA4 protein, human ; Ipilimumab ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2019-09-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.02254
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Article: Contrasting Immunopathogenic and Therapeutic Roles of Granulocyte Colony-Stimulating Factor in Cancer.

Theron, Annette J / Steel, Helen C / Rapoport, Bernardo L / Anderson, Ronald

Pharmaceuticals (Basel, Switzerland)

2020 Volume 13, Issue 11

Abstract: Tumor cells are particularly adept at exploiting the immunosuppressive potential of neutrophils as a strategy to achieve uncontrolled proliferation and spread. Recruitment of neutrophils, particularly those of an immature phenotype, known as granulocytic ...

Abstract	Tumor cells are particularly adept at exploiting the immunosuppressive potential of neutrophils as a strategy to achieve uncontrolled proliferation and spread. Recruitment of neutrophils, particularly those of an immature phenotype, known as granulocytic myeloid-derived suppressor cells, is achieved via the production of tumor-derived granulocyte colony-stimulating factor (G-CSF) and neutrophil-selective chemokines. This is not the only mechanism by which G-CSF contributes to tumor-mediated immunosuppression. In this context, the G-CSF receptor is expressed on various cells of the adaptive and innate immune systems and is associated with induction of T cell polarization towards the Th2 and regulatory T cell (Treg) phenotypes. In contrast to the potentially adverse effects of sustained, endogenous production of G-CSF by tumor cells, stringently controlled prophylactic administration of recombinant (r) G-CSF is now a widely practiced strategy in medical oncology to prevent, and in some cases treat, chemotherapy-induced severe neutropenia. Following an overview of the synthesis, structure and function of G-CSF and its receptor, the remainder of this review is focused on: (i) effects of G-CSF on the cells of the adaptive and innate immune systems; (ii) mechanisms by which this cytokine promotes tumor progression and invasion; and (iii) current clinical applications and potential risks of the use of rG-CSF in medical oncology.
Language	English
Publishing date	2020-11-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph13110406
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Article ; Online: Interactions of HIV and Antiretroviral Therapy With Neutrophils and Platelets.

Madzime, Morris / Rossouw, Theresa M / Theron, Annette J / Anderson, Ronald / Steel, Helen C

Frontiers in immunology

2021 Volume 12, Page(s) 634386

Abstract: Neutrophils are important components of the innate immune system that mediate pathogen defense by multiple processes including phagocytosis, release of proteolytic enzymes, production of reactive oxygen species, and neutrophil extracellular trap ... ...

Abstract	Neutrophils are important components of the innate immune system that mediate pathogen defense by multiple processes including phagocytosis, release of proteolytic enzymes, production of reactive oxygen species, and neutrophil extracellular trap formation. Abnormalities of neutrophil count and function have been described in the setting of HIV infection, with the majority of antiretroviral agents (ARVs), excluding zidovudine, having been reported to correct neutropenia. Questions still remain, however, about their impact on neutrophil function, particularly the possibility of persistent neutrophil activation, which could predispose people living with HIV to chronic inflammatory disorders, even in the presence of virally-suppressive treatment. In this context, the effects of protease inhibitors and integrase strand transfer inhibitors, in particular, on neutrophil function remain poorly understood and deserve further study. Besides mediating hemostatic functions, platelets are increasingly recognized as critical role players in the immune response against infection. In the setting of HIV, these cells have been found to harbor the virus, even in the presence of antiretroviral therapy (ART) potentially promoting viral dissemination. While HIV-infected individuals often present with thrombocytopenia, they have also been reported to have increased platelet activation, as measured by an upregulation of expression of CD62P (P-selectin), CD40 ligand, glycoprotein IV, and RANTES. Despite ART-mediated viral suppression, HIV-infected individuals reportedly have sustained platelet activation and dysfunction. This, in turn, contributes to persistent immune activation and an inflammatory vascular environment, seemingly involving neutrophil-platelet-endothelium interactions that increase the risk for development of comorbidities such as cardiovascular disease (CVD) that has become the leading cause of morbidity and mortality in HIV-infected individuals on treatment, clearly underscoring the importance of unraveling the possible etiologic roles of ARVs. In this context, abacavir and ritonavir-boosted lopinavir and darunavir have all been linked to an increased risk of CVD. This narrative review is therefore focused primarily on the role of neutrophils and platelets in HIV transmission and disease, as well as on the effect of HIV and the most common ARVs on the numbers and functions of these cells, including neutrophil-platelet-endothelial interactions.
Language	English
Publishing date	2021-03-12
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.634386
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Article: ADP-Mediated Upregulation of Expression of CD62P on Human Platelets Is Critically Dependent on Co-Activation of P2Y1 and P2Y12 Receptors.

Anderson, Ronald / Theron, Annette J / Steel, Helen C / Nel, Jan G / Tintinger, Gregory R

Pharmaceuticals (Basel, Switzerland)

2020 Volume 13, Issue 12

Abstract: This study probed the differential utilization of P2Y1 and P2Y12 receptors in mobilizing CD62P (P-selectin) from intracellular granules following activation of human platelets with adenosine 5'-diphosphate (ADP, 100 µmol· ... ...

Abstract	This study probed the differential utilization of P2Y1 and P2Y12 receptors in mobilizing CD62P (P-selectin) from intracellular granules following activation of human platelets with adenosine 5'-diphosphate (ADP, 100 µmol·L
Language	English
Publishing date	2020-11-24
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph13120420
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Article: Comparison of the effects of electronic cigarette vapours and tobacco smoke extracts on human neutrophils

Richards, Guy A / Theron, Annette J / van den Bout, Iman / Anderson, Ronald / Feldman, Charles / van Zyl Smit, Richard / Chang, Ju-Wei / Tintinger, Gregory R

ERJ open research

2023 Volume 9, Issue 3

Abstract: Background: Electronic cigarettes (ECs) are electronic aerosol delivery systems composed of nicotine and various chemicals, which are widely used to facilitate smoking cessation. Although ECs are considered safer than cigarettes, they do, however, ... ...

Abstract	Background: Electronic cigarettes (ECs) are electronic aerosol delivery systems composed of nicotine and various chemicals, which are widely used to facilitate smoking cessation. Although ECs are considered safer than cigarettes, they do, however, contain chemical toxicants, some of which may interact with cells of the host's innate immune system of which neutrophils constitute a key component. Methods: The current study was designed to compare the effects of aqueous EC aerosol extracts (ECEs; with or without nicotine) with those of cigarette smoke extract (CSE) on neutrophil and platelet reactivity Results: Exposure of neutrophils to either ECEs or CSE caused a significant inhibition of ROS generation and elastase release by Conclusions: These observations suggest that ECE aerosols may inhibit some of the immuno-protective activities of neutrophils such as ROS production and elastase release by activated cells, the effect of which was not enhanced by inclusion of nicotine. The inhibitory effects of CSE were significantly more pronounced than those of ECEs, especially so for suppression of NET formation and platelet activation. If operative
Language	English
Publishing date	2023-05-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2827830-6
ISSN	2312-0541
ISSN	2312-0541
DOI	10.1183/23120541.00502-2022
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Article: Dysregulation of systemic soluble immune checkpoints in early breast cancer is attenuated following administration of neoadjuvant chemotherapy and is associated with recovery of CD27, CD28, CD40, CD80, ICOS and GITR and substantially increased levels of PD-L1, LAG-3 and TIM-3.

Rapoport, Bernardo L / Steel, Helen C / Benn, Carol A / Nayler, Simon / Smit, Teresa / Heyman, Liezl / Theron, Annette J / Hlatshwayo, Nomsa / Kwofie, Luyanda L I / Meyer, Pieter W A / Anderson, Ronald

Frontiers in oncology

2023 Volume 13, Page(s) 1097309

Abstract: Neoadjuvant chemotherapy (NAC) may alter the immune landscape of patients with early breast cancer (BC), potentially setting the scene for more effective implementation of checkpoint-targeted immunotherapy. This issue has been investigated in the current ...

Abstract	Neoadjuvant chemotherapy (NAC) may alter the immune landscape of patients with early breast cancer (BC), potentially setting the scene for more effective implementation of checkpoint-targeted immunotherapy. This issue has been investigated in the current study in which alterations in the plasma concentrations of 16 soluble co-stimulatory and co-inhibitory, immune checkpoints were measured sequentially in a cohort of newly diagnosed, early BC patients (n=72), pre-treatment, post-NAC and post-surgery using a Multiplex
Language	English
Publishing date	2023-03-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1097309
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Article: Electronic cigarettes: where to from here?

Theron, Annette J / Feldman, Charles / Richards, Guy A / Tintinger, Gregory R / Anderson, Ronald

Journal of thoracic disease

2020 Volume 11, Issue 12, Page(s) 5572–5585

Abstract: Although the usage of electronic (e)-cigarettes (EC) and similar devices has gained in popularity as an apparent smoking cessation strategy, serious concerns are emerging in relation to both the efficacy of this strategy, as well as the inappropriate use ...

Abstract	Although the usage of electronic (e)-cigarettes (EC) and similar devices has gained in popularity as an apparent smoking cessation strategy, serious concerns are emerging in relation to both the efficacy of this strategy, as well as the inappropriate use of these devices. While the comparative safety of e-cigarettes is based on the reasonable contention that the levels of inhaled toxicants present in the aerosols generated by these devices are considerably lower than those present in tobacco smoke, the perception that they are indeed relatively risk-free is being challenged on several fronts. Notwithstanding lack of convincing evidence of efficacy as a superior smoking cessation strategy, foremost among emerging concerns is the increasing use of electronic nicotine-delivery devices by young never-smokers. Other concerns include increasing levels of sophistication in the design and capacity of these devices in relation to nicotine content and delivery, the potential threat of manipulation of the contents of e-liquids, as well as other additives such as illicit drugs and other potentially toxic agents that can be vaporised. These issues, together with the potential risks to respiratory health, specifically "e-cigarette or vaping product use-associated lung injury" represent the major thrusts of this review.
Language	English
Publishing date	2020-01-22
Publishing country	China
Document type	Journal Article ; Review
ZDB-ID	2573571-8
ISSN	2077-6624 ; 2072-1439
ISSN (online)	2077-6624
ISSN	2072-1439
DOI	10.21037/jtd.2019.11.82
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Article ; Online: Role of the Neutrophil in the Pathogenesis of Advanced Cancer and Impaired Responsiveness to Therapy.

Rapoport, Bernardo L / Steel, Helen C / Theron, Annette J / Smit, Teresa / Anderson, Ronald

Molecules (Basel, Switzerland)

2020 Volume 25, Issue 7

Abstract: Notwithstanding the well-recognized involvement of chronic neutrophilic inflammation in the initiation phase of many types of epithelial cancers, a growing body of evidence has also implicated these cells in the pathogenesis of the later phases of cancer ...

Abstract	Notwithstanding the well-recognized involvement of chronic neutrophilic inflammation in the initiation phase of many types of epithelial cancers, a growing body of evidence has also implicated these cells in the pathogenesis of the later phases of cancer development, specifically progression and spread. In this setting, established tumors have a propensity to induce myelopoiesis and to recruit neutrophils to the tumor microenvironment (TME), where these cells undergo reprogramming and transitioning to myeloid-derived suppressor cells (MDSCs) with a pro-tumorigenic phenotype. In the TME, these MDSCs, via the production of a broad range of mediators, not only attenuate the anti-tumor activity of tumor-infiltrating lymphocytes, but also exclude these cells from the TME. Realization of the pro-tumorigenic activities of MDSCs of neutrophilic origin has resulted in the development of a range of adjunctive strategies targeting the recruitment of these cells and/or the harmful activities of their mediators of immunosuppression. Most of these are in the pre-clinical or very early clinical stages of evaluation. Notable exceptions, however, are several pharmacologic, allosteric inhibitors of neutrophil/MDSC CXCR1/2 receptors. These agents have entered late-stage clinical assessment as adjuncts to either chemotherapy or inhibitory immune checkpoint-targeted therapy in patients with various types of advanced malignancy. The current review updates the origins and identities of MDSCs of neutrophilic origin and their spectrum of immunosuppressive mediators, as well as current and pipeline MDSC-targeted strategies as potential adjuncts to cancer therapies. These sections are preceded by a consideration of the carcinogenic potential of neutrophils.
MeSH term(s)	Animals ; Cell Transformation, Neoplastic ; Disease Management ; Disease Susceptibility ; Host-Pathogen Interactions ; Humans ; Immunomodulation ; Inflammation/complications ; Myeloid-Derived Suppressor Cells/immunology ; Myeloid-Derived Suppressor Cells/metabolism ; Neoplasm Metastasis ; Neoplasm Staging ; Neoplasms/drug therapy ; Neoplasms/etiology ; Neoplasms/metabolism ; Neoplasms/pathology ; Neutrophils/drug effects ; Neutrophils/immunology ; Neutrophils/metabolism ; Oxidation-Reduction ; Oxidative Stress ; Treatment Outcome
Language	English
Publishing date	2020-04-01
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules25071618
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