A5081797509- Lymphoma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Chronic Lymphocytic Leukemia Research
- Viral-associated cancers and disorders
- CNS Lymphoma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Circular RNAs in diseases
- MicroRNA in disease regulation
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Treatments and Mutations
- Immunotherapy and Immune Responses
- Acute Myeloid Leukemia Research
- Cancer Genomics and Diagnostics
- Mesenchymal stem cell research
- Ovarian cancer diagnosis and treatment
- Cardiac, Anesthesia and Surgical Outcomes
- Immune cells in cancer
- Pancreatic and Hepatic Oncology Research
- Acute Lymphoblastic Leukemia research
- Protein Degradation and Inhibitors
- Sarcoma Diagnosis and Treatment
- Eosinophilic Disorders and Syndromes
- Glioma Diagnosis and Treatment
Princess Alexandra Hospital
2016-2025
The University of Queensland
2015-2024
Translational Research Institute
2015-2024
Mater Research
2019-2024
St. James's Hospital
2021
Trinity College Dublin
2021
Ollscoil na Gaillimhe – University of Galway
2017-2020
Arena Pharmaceuticals (United States)
2020
Queen's Medical Centre
2016-2018
St. Michael's Hospital
2017
Although microRNAs (miRNA) show potential as diagnostic biomarkers in cancer, their role circulating cell-free disease response remains unknown. Candidate miRNA for classical Hodgkin lymphoma (cHL) might arise from Hodgkin-Reed-Sternberg (HRS) cells and/or nonmalignant tumor-infiltrating cells. HRS are sparse within the diseased node, embedded a benign microenvironment, composition of which is distinct that seen healthy lymph nodes.Microarray profiling more than 1,000 human miRNAs 14 cHL...
Understanding the immunobiology of 15% to 30% patients with follicular lymphoma (FL) who experience progression disease within 24 months (POD24) remains a priority. Solid tumors low levels intratumoral immune infiltration have inferior outcomes. It is unknown whether similar relationship exists between POD24 in FL.Digital gene expression using custom code set-five effector, six checkpoint, one macrophage molecules-was applied discovery cohort early- and advanced-stage FL (n = 132). T-cell...
Abstract Blockade of the PD-1 axis has modest efficacy in diffuse large B-cell lymphoma (DLBCL), but data regarding LAG3 are sparse. The impact digital gene expression was tested 309 patients with DLBCL treated standard chemoimmunotherapy. Cellular distribution protein determined by immunohistochemistry and flow cytometry. In tumor-infiltrating lymphocytes (TILs), highest on CD4+ regulatory T cells (Tregs) also highly expressed CD8+ compared non-Tregs (both P = .008). LAG3high TILs were...
Abstract Purpose: Candidate circulating disease response biomarkers for classical Hodgkin lymphoma (cHL) might arise from Hodgkin–Reed–Sternberg (HRS) cells or nonmalignant tumor-infiltrating cells. HRS are sparse within the diseased node, whereas benign CD163+ M2 tissue-associated macrophages (TAM) prominent. malignant node may be prognostic, but there is no data on serum CD163 (sCD163). The HRS-specific protein sTARC shows promise as a biomarker. Tumor-specific and have not been compared...
Purpose: To investigate the relationship between intra-tumoral T-cell receptor (TCR) repertoire and tumor microenvironment (TME) in de novo diffuse large B-cell lymphoma (DLBCL) impact of TCR on survival.Experimental Design: We performed high-throughput unbiased TCRβ sequencing a population-based cohort 92 patients with DLBCL treated conventional (i.e., non-checkpoint blockade) frontline "R-CHOP" therapy. Key immune checkpoint genes within TME were digitally quantified by nanoString. The...
Primary central nervous system (pCNS) posttransplant lymphoproliferative disorder (PTLD) is a complication of solid organ transplantation characterized by poor outcome. In contrast to systemic PTLD, Epstein-Barr virus (EBV)-association pCNS PTLD almost universal, yet viral and cellular data are limited. To identify differences in the pattern EBV-association we analyzed expression latent lytic EBV transcripts microRNAome nine (eight EBV-associated) 16 samples EBV-associated). Notably although...
Abstract Objective Epstein‐Barr virus‐positive diffuse large B‐cell lymphoma (EBV ‐pos DLBCL) is a recently identified entity. Data regarding outcome to frontline immuno‐chemotherapy are conflicting. Although the prognostic impact of tumour microenvironment (TME) in EBV ‐neg DLBCL well‐established, it remains untested whether TME influences survival DLBCL. There no data with new digital gene expression technologies that simultaneously interrogate virus, B cells and (TME). Methods We used...
Follicular lymphoma (FL) treatment initiation is largely determined by tumor burden and symptoms. In the pre-rituximab era, Group d’Etude des Lymphomes Folliculaires (GELF) developed widely adopted criteria to identify high FL patients harmonize clinical trial populations. The utilization of GELF (GELFc) in routine therapeutic decision- making poorly described. This multicenter retrospective study evaluated patterns GELFc at presentation decision-making newly diagnosed, advanced-stage...
Tumour necrosis factor (TNF) is a primary mediator of inflammatory processes by facilitating cell death, immune activation and triggering inflammation. In the cancer context, research has revealed TNF as multifaceted cytokine that can be both pro- or anti-tumorigenic depending on what context observed. We explore plethora ways its receptors manipulate functional phenotypic characteristics in tumour microenvironment (TME) cells cells, promoting either elimination progression. Here, we discuss...
Follicular lymphoma (FL) outcomes are heavily influenced by host immune activity with anti-tumor mitigated PD-1/PD-L1 pathway engagement. Combination CD20-directed therapy plus PD-1 inhibition (PD-1i) increases T-cell tumor killing and NK-cell antibody-dependent cell cytotoxicity (ADCC). Mounting evidence supports immune-priming using PD-1i before cancer-directed agents. Our multicentre, open-label, phase II 1st FLOR study (NCT03245021) enrolled 39 previously-untreated advanced-stage FL...
In 40% of cases classical Hodgkin lymphoma (cHL), Epstein-Barr virus (EBV) latency-II antigens [EBV nuclear antigen 1 (EBNA1)/latent membrane protein (LMP)1/LMP2A] are present (EBV(+) cHL) in the malignant cells and presentation is intact. Previous studies have shown consistently that HLA-A*02 protective EBV(+) cHL, yet its role disease pathogenesis unknown. To explore basis for this observation, gene expression was assessed 33 cHL nodes. Interestingly, CD8 LMP2A were correlated strongly...
Abstract Polatuzumab vedotin (Pola) is an approved therapy in combination with rituximab and bendamustine for relapsed or refractory diffuse large B‐cell lymphoma (RR‐DLBCL) based on positive results of the landmark phase II randomised G029365 trial. However, trial many novel therapies RR‐DLBCL have not been replicated routine care cohorts, as patient populations are heterogeneous eligibility increasingly restrictive. We evaluated outcomes from pola ± patients enrolled a compassionate access...
Abstract Recently, nontumor specific circulating DNA was shown to be elevated in a broad range of lymphomas, implicating role as potential biomarker. Epstein‐Barr virus' (EBV) presence within proportion lymphomas implies EBV‐DNA has lymphoma‐specific disease response However, application would restricted EBV‐associated lymphomas. Neither detailed comparison been performed versus nonspecific biomarkers nor have the kinetics during treatment established, and optimal methodology remains...
To test the utility of circulating Lactate Dehydrogenase (LDH) to absolute lymphocyte count (ALC) ratio (LAR) predict outcome conventional first-line chemo-immunotherapy in Diffuse Large B-cell Lymphoma (DLBCL), and investigate its correlation tumour immune microenvironment (TME).A population based cohort 210 patients (median age: 64, range 18-90 years) with median follow up 3.8 years was analysed. All were treated R-CHOP, no immunosuppression related cases included. Tissue for nanoString...
Summary De novo diffuse large B‐cell lymphoma (DLBCL) presenting with synchronous central nervous system (CNS) and systemic disease (synDLBCL) is not well described excluded from clinical trials. We performed a retrospective analysis of 80 synDLBCL patients treated across 10 Australian UK centres. Of these patients, 96% had extranodal disease. CNS‐directed treatment combination intravenous cytarabine high‐dose methotrexate (“CNS‐intensive”) ( n = 38) was associated favourable survival...
Summary Epstein–Barr virus (EBV)‐associated lymphomas cover a range of histological B‐ and T‐cell non‐Hodgkin Hodgkin lymphoma subtypes. The role EBV on B‐cell malignant pathogenesis its impact the tumour microenvironment are intriguing but incompletely understood. Both International Consensus Classification (ICC) 5th Edition World Health Organization (WHO‐HAEM5) proposals give prominence to distinct clinical, prognostic, genetic microenvironmental features in lymphoproliferative disorders....