A5007330428- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Cancer Research and Treatments
- Adenosine and Purinergic Signaling
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- Immune cells in cancer
- Cytokine Signaling Pathways and Interactions
- Macrophage Migration Inhibitory Factor
- HER2/EGFR in Cancer Research
- Peptidase Inhibition and Analysis
- Galectins and Cancer Biology
- Cancer Mechanisms and Therapy
- Psoriasis: Treatment and Pathogenesis
- IL-33, ST2, and ILC Pathways
- Chemokine receptors and signaling
- Colorectal Cancer Treatments and Studies
- Phagocytosis and Immune Regulation
- Colorectal and Anal Carcinomas
- Nanoplatforms for cancer theranostics
- Radiomics and Machine Learning in Medical Imaging
- Bladder and Urothelial Cancer Treatments
QIMR Berghofer Medical Research Institute
2014-2024
The University of Queensland
2013-2022
Royal Brisbane and Women's Hospital
2020
Queensland Health
2020
The University of Melbourne
2009-2019
Peter Doherty Institute
2019
Peter MacCallum Cancer Centre
2005-2014
Indiana University School of Medicine
2014
Immunité et Cancer
2014
Brisbane School of Theology
2014
Abstract Immunotherapy has recently entered a renaissance phase with the approval of multiple agents for treatment cancer. stands ready to join traditional modalities, including surgery, chemotherapy, radiation, and hormone therapy, as pillar cancer treatment. Although immunotherapy begun have success in advanced treatment, its scheduling efficacy surgery treat earlier stages prevent distant metastases not been systematically examined. Here, we used two models spontaneously metastatic breast...
Abstract Strategies to activate and rescue exhausted tumor-specific T cells, including the use of monoclonal antibodies (mAb) that block negative costimulatory receptors CTLA-4 PD-1 are proving very effective, but TIM3 has been relatively neglected as a target. Here we report an extensive characterization therapeutic activity mechanism action anti-mouse mAb against experimental carcinogen-induced tumors. For first time specifically define antitumor anti-TIM3 requiring IFN-γ producing CD8+...
Coinhibitory receptors are critical for the maintenance of immune homeostasis. Upregulation these on effector T cells terminates cell responses, while their expression Tregs promotes suppressor function. Understanding function coinhibitory in and is crucial, as therapies that target currently at forefront treatment strategies cancer other chronic diseases. Ig ITIM domain (TIGIT) a recently identified receptor found surface variety lymphoid cells, its role regulation just beginning to be...
Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor-2 (HER2/ErbB-2), has become the mainstay of treatment for HER2-positive breast cancer. Nevertheless, its exact mechanism action not been fully elucidated. Although several studies suggest that Fc receptor-expressing immune cells are involved in trastuzumab therapy, relative contribution lymphocyte-mediated cellular cytotoxicity and antitumor cytokines remains unknown. We report here anti–ErbB-2 mAb therapy is...
CD4+CD25+ regulatory T cells (Treg) that suppress cell-mediated immune responses may also regulate other arms of an effective response. In particular, in this study we show Treg directly inhibit NKG2D-mediated NK cell cytotoxicity vitro and vivo, effectively suppressing tumor rejection. vitro, were shown to cytolysis largely by a TGF-beta-dependent mechanism independently IL-10. Adoptively transferred suppressed antimetastatic function RAG-1-deficient mice. Depletion before activation via...
CD73 is a cell-surface enzyme that suppresses immune responses by producing extracellular adenosine. In this study, we employed gene-targeted mice to investigate the role of host-derived on antitumor immunity and tumor cell metastasis. We found ablation significantly suppressed growth ovalbumin-expressing MC38 colon cancer, EG7 lymphoma, AT-3 mammary tumors, B16F10 melanoma. The protective effect deficiency primary tumors was dependent CD8(+) T cells associated with an increased frequency...
Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting immunogenicity of developing tumors. Although full depends on innate and adaptive immunity, it remains unclear whether immunity alone capable immunoediting. To determine system can edit tumor in absence we compared incidence 3′methylcholanthrene-induced sarcomas syngeneic wild-type, RAG2−/−, RAG2−/−x γc−/− mice. We found that could manifest activity immunity. This required natural killer...
T-cell immunoglobulin mucin 3 (TIM3) is an inhibitory molecule that has emerged as a key regulator of dysfunctional or exhausted CD8+ T cells arising in chronic diseases such cancer. In addition to cells, highly suppressive regulatory (Tregs) represent significant barrier against the induction antitumor immunity. We have found majority intratumoral FOXP3+ Tregs express TIM3. TIM3+ co-express PD-1, are and comprise specialized subset tissue rarely observed peripheral tissues blood...
Abstract Tumor-bearing individuals have been reported to harbor increased numbers of Foxp3+ regulatory T cells (Treg), which prevent the development efficient antitumor immune responses. Thus, Treg depletion has already tested as a promising therapeutic approach in various animal models and entered clinical trials. However, use nonspecific targeting agents such CD25 depleting antibodies, addition CD25+ Tregs also deplete recently activated effector cells, potentially masked tremendous...
Adenosine targeting is an attractive new approach to cancer treatment, but no clinical study has yet examined adenosine inhibition in oncology despite the safe profile of A2A receptor inhibitors (A2ARi) Parkinson disease. Metastasis main cause cancer-related deaths worldwide, and therefore we have studied experimental spontaneous mouse models melanoma breast metastasis demonstrate efficacy mechanism a combination A2ARi with anti-PD-1 monoclonal antibody (mAb). This significantly reduces...