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.
In 2016 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. Clinically, our study has now spurred many of our clinical colleagues to undertake new clinical trials in many cancer types to compare the efficacy of neoadjuvant compare to adjuvant immunotherapies. Excitingly, initial clinical trial studies reported promising data suggesting that neoadjuvant compared to adjuvant immunotherapies further improved clinical outcomes. Nevertheless, there are many key questions to be answered, including 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 may allow us to further improve the efficacy of immunotherapies in general.
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 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.
- Targeting immunosuppressive adenosine in cancer
- Dissecting the immunological mechanisms underlying the efficacy of neoadjuvant cancer immunotherapy
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