Scott Andrew Fisher

Scott Andrew Fisher
University of Western Australia | UWA · National Centre for Asbestos Related Diseases (NCARD)

PhD

About

42
Publications
5,702
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643
Citations
Citations since 2017
22 Research Items
456 Citations
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Introduction
Research interests: Mesothelioma: host genetics, fibre carcinogenesis, biological pathways associated with development. Voluntary exercise and an adjunctive supportive therapy. Tumour immunology/biology: How to induce effective anti-cancer immunity. cancer vaccines, immune checkpoint blockade, combination therapies.

Publications

Publications (42)
Article
Full-text available
While chemotherapy remains the first-line treatment for many cancers, it is still unclear what distinguishes responders from non-responders. Here, we characterize the chemotherapy-responsive tumor microenvironment in mice, using RNA sequencing on tumors before and after cyclophosphamide, and compare the gene expression profiles of responders with p...
Article
Introduction: Malignant pleural mesothelioma (MPM) is a fatal cancer type that affects the membranes lining the lungs and is causally associated with asbestos exposure. Despite the effectiveness of conventional anti-cancer treatment, its prognosis remains very poor. We previously demonstrated a significant survival benefit for PD-L1 blockade in pre...
Article
Full-text available
Chemotherapy has historically been the mainstay of cancer treatment, but our understanding of what drives a successful therapeutic response remains limited. The diverse response of cancer patients to chemotherapy has been attributed principally to differences in the proliferation rate of the tumor cells, but there is actually very little experiment...
Article
Full-text available
Antibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4 (CTLA‐4) and the programmed cell death protein 1/ligand 1 (PD-1/PD-L1) are now a treatment option for multiple cancer types. However, as a monotherapy, objective responses only occur in a minority of patients. Chemotherapy is widely used in combination with immune ch...
Article
Full-text available
Surgical resection of cancer remains the frontline therapy for millions of patients annually, but post-operative recurrence is common, with a relapse rate of around 45% for non-small cell lung cancer. The tumour draining lymph nodes (dLN) are resected at the time of surgery for staging purposes, and this cannot be a null event for patient survival...
Article
Full-text available
Thoracic cancers pose a significant global health burden. Immune checkpoint blockade therapies have improved treatment outcomes, but durable responses remain limited. Understanding how the host immune system interacts with a developing tumor is essential for the rational development of improved treatments for thoracic malignancies. Recent technical...
Article
Full-text available
Malignant pleural mesothelioma (MPM) is an aggressive cancer that is causally associated with previous asbestos exposure in most afflicted patients. The prognosis of patients remains dismal, with a median overall survival of only 9–12 months, due to the limited effectiveness of any conventional anti-cancer treatment. New therapeutic strategies are...
Article
Full-text available
Immune checkpoint therapy (ICT) results in durable responses in individuals with some cancers, but not all patients respond to treatment. ICT improves CD8+ cytotoxic T lymphocyte (CTL) function, but changes in tumor antigen-specific CTLs post-ICT that correlate with successful responses have not been well characterized. Here, we studied murine tumo...
Article
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Objective: There is substantial evidence that exercise can safely reduce the risk of cancer and improve survival in different human cancer populations. Long latency periods associated with carcinogen-induced cancers like asbestos induced mesothelioma provide an opportunity to implement exercise as an intervention to delay or prevent disease develo...
Conference Paper
Full-text available
Objective: Spontaneous neo-antigen specific immune responses are rare in animals and humans. Our AB1 model, one of the few induced by a natural human carcinogen, has several. Given that current immunotherapies rely on unleashing responses to existing tumour neo-antigens, we evaluated the capacity of such responses to inform subsequent therapies, de...
Preprint
Full-text available
Objective There is substantial evidence that exercise can safely reduce the risk of cancer and improve survival in different human cancer populations. Long latency periods associated with carcinogeninduced cancers like asbestos induced mesothelioma provide an opportunity to implement exercise as an intervention to delay or prevent disease developme...
Preprint
Full-text available
Objective: There is substantial evidence that exercise can safely reduce the risk of cancer and improve survival in different human cancer populations. Long latency periods associated with carcinogen‑induced cancers like asbestos induced mesothelioma provide an opportunity to implement exercise as an intervention to delay or prevent disease develop...
Article
Full-text available
Non-small cell lung cancer (NSCLC) causes 19% of all Australian cancer deaths, with a 5-year survival post-resection of around 60%. Post-operative recurrence is due to metastases that were undetectable pre-operatively, or growth of microscopic locoregional residual disease. However, post-operative imaging modalities typically only detect more advan...
Chapter
Our current understanding of mesothelioma in terms of disease induction, development, and treatment is underpinned by decades of basic laboratory science. In this chapter, we discuss the tools that have been developed to aid our understanding of mesothelioma such as cell lines and animal models. We then go on to detail the current use and understan...
Conference Paper
Full-text available
Exercise medicine is a relatively new but exciting field in cancer care. There is substantial evidence that exercise can reduce the risk of many cancers and improve survival in some cancers, including mesothelioma. Exercise during and after conventional therapies has been shown to be safe, improve symptom control, quality of life (QOL) and fitness,...
Article
Full-text available
Objectives The global burden of asbestos-related diseases (ARDs) is significant, and most of the world’s population live in countries where asbestos use continues. We examined the gaps between ARD research and suggestions of WHO and the International Labour Organization on prevention. Methods From the Web of Science, we collected data on all artic...
Article
Full-text available
Mesothelioma is an aggressive asbestos induced cancer with extremely poor prognosis and limited treatment options. Immune checkpoint blockade (ICPB) has demonstrated effective therapy in melanoma and is now being applied to other cancers, including mesothelioma. However, the efficacy of ICPB and which immune checkpoint combinations constitute the b...
Conference Paper
Full-text available
Objectives: Asbestos comprises six naturally occurring silicate minerals which have the common characteristic of being long (roughly 1:20 aspect ratio), thin fibrous crystals, with each visible fibre composed of millions of microscopic 'fibrils' that can be released by abrasion and other processes. Additionally, there are other non-asbestos mineral...
Article
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Introduction Regulatory T cells (Treg) play an important role in suppressing anti‐ immunity and their depletion has been linked to improved outcomes. To better understand the role of Treg in limiting the efficacy of anti‐cancer immunity, we used a Diphtheria toxin (DTX) transgenic mouse model to specifically target and deplete Treg. Methods Tumor...
Article
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Treatment of lung cancer remains a challenge, and lung cancer is still the leading cause of cancer-related mortality. Immunotherapy has previously failed in lung cancer but has recently emerged as a very effective new therapy, and there is now growing worldwide enthusiasm in cancer immunotherapy. We summarize why immune checkpoint blockade therapie...
Article
Full-text available
A key to improving cancer immunotherapy will be the identification of tumor-specific ‘neo-antigens’ that arise from mutations and augmenting the resultant host immune response. In this study we identified single nucleotide variants (SNV) from RNA sequencing of asbestos induced murine mesothelioma cell lines, AB1 and AB1-HA. Using the NetMHCpan 2.8...
Article
Full-text available
Tumor debulking surgery followed by adjuvant chemotherapy or radiotherapy is a standard treatment for many solid malignancies. Although this approach can be effective, it often has limited success against recurrent or metastatic cancers and new multimodality approaches are needed. Adjuvant immunotherapy is another potentially effective approach. We...
Article
Full-text available
Given the impressive efficacy of immune checkpoint blockade in thoracic malignancies, and the recently discovered immune-stimulating properties of many cytotoxic drugs, a logical next step would be to combine these treatments. However, the rational design of clinical trials investigating these combinations is hampered by a lack of knowledge regardi...
Conference Paper
Full-text available
Targeted depletion of regulatory T cells is important for effective adjuvant immunotherapy of murine mesothelioma Scott A Fisher1,2,*, Andrea Khong1,2, Wayne Aston1,2, Justin Simms1,2, Thomas Casey1,2, Bruce W. Robinson1,2, W. Joost Lesterhuis1,2 , Richard A. Lake1,2 1National Centre for Asbestos Related Diseases (NCARD), Perth, Australia. 2Schoo...
Article
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Cross-presentation of tumor antigen is essential for efficient priming of nave CD8 + T lymphocytes and induction of effective anti-tumor immunity. We hypothesized that the subcellular location of a tumor antigen could affect the efficiency of cross-presentation, and hence the outcome of anti-tumor responses to that antigen. We compared cross-presen...
Article
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Background This study was conducted to determine if anti-tumor vaccination administered prior to partial debulking surgery could improve survival using a murine solid tumour model.Methods Tumor incidence and survival rates were compared in mice bearing subcutaneous AB1-HA mesothelioma tumors that received either sham surgery, debulking surgery or v...
Article
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Most anticancer therapies including immunotherapies are given systemically; yet therapies given directly into tumorsmay be more effective, particularly those that overcomenatural suppressive factors in the tumor microenvironment.The“TrojanHorse” approach of intratumoural delivery aims to promote immune-mediated destruction by inducing microenvironm...
Conference Paper
Full-text available
Combining Prime-Boost Anti-tumour Vaccination with Debulking Surgery for the Treatment of Solid Tumours. Scott A Fisher, Amanda L Cleaver, Andrea Khong, Theresa Connor, Ben Wylie, Daphne Lakhiani, Catherine Boylen Bruce W Robinson and Richard Lake. National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology University of Wes...
Conference Paper
Full-text available
Combining Prime-Boost Anti-tumour Vaccination with Debulking Surgery for the Treatment of Malignant Mesothelioma Scott A Fisher, Amanda L Cleaver, Andrea Khong, Theresa Connor, Ben Wylie, Daphne Lakhiani, Bruce W Robinson and Richard A. Lake. National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology University of Western...
Article
Full-text available
Malignant mesothelioma (MM) is a highly aggressive, incurable asbestos-induced cancer for which treatment options are limited. Surgical resection can reduce tumour burden, but patients ultimately succumb to disease due to reoccurrence of unresectable tumour, highlighting the need for new treatment modalities. In this study we describe the use of an...
Conference Paper
Full-text available
The development of anti cancer vaccines has so far met with disappointing results. This is in part associated with the issues of tolerance (tumour antigens are often derived from self proteins) and immunodominance; even when tumour antigens are expressed in the context of viral vectors, the resulting immune response is usually dominated by the much...
Article
Murine AIDS (MAIDS) is a pathology induced by the LP-BM5 murine leukaemia virus mixture in susceptible strains of mice such as C57BL/6J resulting in lymphoproliferation and progressive immunodeficiency. The etiologic agent of this pathology is BM5d, a replication defective virus. BM5e is a replication competent virus in the viral mixture that funct...
Article
Full-text available
Liver fibrosis was correlated with immunological parameters. Peripheral blood mononuclear cells (PBMCs) from patients with low fibrosis scores had fewer interferon (IFN)–γ–producing cells than did patients with higher fibrosis scores, when stimulated with hepatitis C virus (HCV) core antigen. Irrespective of liver fibrosis score, cells from all cyt...
Article
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To determine whether APC function or "arming" of CTL for lytic function are the points at which Ags from a nonimmunogenic tumor fail to induce an effective immune response, we established a murine tumor model that expressed intracellular OVA and selected a clone (cOVA-9) that remained susceptible to lysis by specific CD8(+) T cells throughout tumor...
Article
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A substantial body of literature has described weak antitumor CTL responses in tumor-bearing hosts, and a number of authors have suggested that tumor tissue in some way sequesters antigen from the immune system, a failure of the tumor-specific immune response largely attributable to "ignorance." To evaluate this in a tumor model, we stably transfec...
Conference Paper
A substantial body of literature has described weak antitumor CTL responses in tumor-bearing hosts, and a number of authors have suggested that tumor tissue in some way sequesters antigen from the immune system, a failure of the tumor-specific immune response largely attributable to "ignorance." To evaluate this in a tumor model, we stably transfec...
Article
Full-text available
Salicylate and acetylsalicylate slightly increased fluoroquinolone resistance in ciprofloxacin-susceptible and -resistant Staphylococcus aureus. Salicylate allowed a greater number of cells from ciprofloxacin-susceptible and -resistant strains to survive on high fluoroquinolone concentrations. Salicylate also increased the frequency with which a su...

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Projects

Projects (2)
Project
Use our well characterised mouse model of mesothelioma to; 1) Assess immune checkpoint molecule expression on tumour resident lymphocytes. 2) Test the efficacy of individual and combination ICPB therapy to induce effective anti-tumour immunity in s.c. and orthotopic models. 3) Evaluate the changes to immune cell phenotype, function related to treatment
Project
Identify modifier genes associated with asbestos induced mesothelioma development following asbestos exposure. Generate CC-MexTAg progeny mice and assess overall survival, latency and disease progression after asbestos exposure. Identify candidate modifier genes using GeneMiner bioinformatic pipeline Validate candidate gene expression in CC-MexTAg mice, identify potential biological pathways/druggable targets. Interrogate human mesothelioma GWAS data sets.