The Cancer Immunoregulation and Immunotherapy Laboratory investigates how tumour-induced immunosuppression controls the three phases of cancer immunoediting. In particular, the laboratory has a strong interest in investigating the immunosuppressive role of regulatory T cells (Tregs), T cell anergy/exhaustion, 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 effective in the eradicating of metastases in the context of cancer surgery. Our study has now spurred many of our colleagues to undertake new clinical trials in many cancer types to compare the efficacy of neoadjuvant to adjuvant immunotherapies. Excitingly, initial clinical trial studies reported promising data suggesting neoadjuvant compared to adjuvant immunotherapies further improved clinical outcomes. 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 selective targeting and further improvements of immunotherapies in general.
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 (antitumour efficacy vs immune-related adverse events (irAEs)) of antibodies targeting various immunomodulatory receptors to be simultaneously assessed for the first time. This model may be used to preclinically assess the therapeutic window of novel immunotherapy combinations in different tumour types. This will aid clinicians and pharmaceutical companies weigh up their risk/cost–benefit profile.
We gratefully acknowledge the support of the following funding agencies: