- 19 September 2019
1:00 pm - 2:00 pm
THURSDAY 19 SEPTEMBER 2019, 1.00 PM
Auditorium, Level 6, Bancroft Building
Inhibitory immune receptors: Are we barking up the wrong tree?
Dr Tobias Bald
Oncology and Cellular Immunology
QIMR Berghofer Medical Research Institute
The upregulation of inhibitory immune receptors is a major driver of immune escape in cancer. In contrast, little is known about the regulation of immune cell activating receptors within the tumor microenvironment. Using genetically engineered mice, pre-clinical models of cancer and patient samples, we describe that tumor cell-derived CD155 downregulates the co-stimulatory receptor CD226 in mouse and human CD8+ T cells, leading to profound loss of effector functions. Mechanistically, CD155 drives internalisation of CD226 through phosphorylation of tyrosine 319 (CD226Y319). Accordingly, T cells harbouring a mutation in Y319 showed increased CD226 surface expression and effector function associated with improved efficacy of cancer immunotherapies. Clinically, the number of CD226+CD8+ T cells in pre-treatment samples from melanoma patients significantly correlated with response to immunotherapy and survival. In summary, we unravelled a new paradigm in which tumor cells escape destruction by T cells through downregulation of the activating receptor CD226.v
Dr Tobias Bald is a Team Head in the Department of Immunology at QIMR Berghofer Medical Research Institute. He obtained his MSc and PhD in Molecular Biomedicine at the University of Bonn where he received training in tumour immunology and tumour biology. After a post-doc in Magdeburg, Germany, he joined the laboratory of Prof Mark Smyth. Over the last years Dr Bald focused on the balance between anti-tumour immunity and pro-tumorigenic inflammatory responses in the context of cancer. Dr Bald showed that targeted activation of the type I IFN system with immunostimulatory RNA in combination with blockade of immune inhibitory receptors serve as a rational strategy to expose immune cell-poor melanomas to cellular immune surveillance. Furthermore, Dr Bald established and characterized novel genetically engineered mouse melanoma model systems to experimentally investigate the interaction between innate immune, endothelial and melanoma cells. Currently, Dr Bald is studying the role of innate immune cells during tumour development and immunotherapy.