The Teng Cancer Immunoregulation and Immunotherapy Laboratory investigates how tumour-induced immunosuppression controls the three phases of cancer immunoediting. In particular, my laboratory has a strong interest in investigating the immunosuppressive role of regulatory T cells (Tregs), T cell anergy/exhaustion (mediated by checkpoint receptors), the cytokine IL-23 and its associated cytokine family and immunosuppressive metabolites (adenosine) in the local tumour microenvironment using experimental and de novo mouse models of cancer.
A major focus of the laboratory currently lies in determining the optimal scheduling of immunotherapy to maximise its anti-tumour efficacy. Recently, our group provided the first demonstration in pre-clinical tumor models that neoadjuvant compared to adjuvant immunotherapies were more efficacious in the eradicating of metastases in the context of cancer surgery. This study now raises many key questions about the mechanism of long-lasting immunity created by neoadjuvant immunotherapy, the role of the primary tumor, the possible discovery of new biomarkers in the tumor and blood, and the potentially shortened treatment schedule that may deliver cheaper and safer alternatives for cancer patients. Ongoing work in the laboratory now aims to understand the key mechanism and pathways that are activated and/or required by neoadjuvant immunotherapy which may allow for their selective targeting and thus further improve the efficacy of immunotherapies. In parallel, our study has now spurred many of our clinical colleagues to undertake new clinical trials to compare the efficacy of neoadjuvant compare to adjuvant immunotherapies.
Currently, the next frontier in cancer immunotherapy lies in combination approaches and this can potentially benefit a greater proportion of patients with cancer. Although new combination immunotherapies induce better efficacy, they can potentially induce severe immune-related adverse events (irAE) in humans and can lead to discontinuation of treatment and can result in fatalities if not promptly treated. Clinicians are currently faced with the dilemma of what combination immunotherapies to test in different cancers. The laboratory has also recently developed a preclinical mouse model that allows the therapeutic index (antitumor efficacy vs immune-related adverse events (irAEs)) of antibodies targeting various immunomodulatory receptors to be simultaneously assessed for the first time. Filling a need, this mouse model may be used to preclinically assess the therapeutic window of novel immunotherapy combinations in different tumor types to aid clinicians and pharmaceutical companies weigh up their risk/cost–benefit profile. Furthermore, our model offers an opportunity to dissect whether the molecular pathways governing the development of antitumor immunity and irAEs are related or distinct to allow more specific targeting.
Group Leader: Dr Michele Teng
- Dr Michele Teng, Group Leader
- Dr Stacey Allen, Research Assistant
- Dr Jing Liu, Research Officer
- Heidi Harjunpaa, PhD Student
- Juming Yan, PhD student
- Dr Liam Town, Laboratory Manager
- Kate Elder, Scientific Technical Officer
- Dr Elizabeth Ahern, PhD Student
- Jake O’Donnell, PhD Student
- Targeting immunosuppressive adenosine in cancer
- Dissecting the immunological mechanisms underlying the efficacy of neoadjuvant cancer immunotherapy
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