Most solid tumours contain cells that are poorly oxygenated, and these hypoxic tumour cells are refractory to a variety of cancer treatments including radiation therapy and chemotherapy.  Not only are hypoxic cells the most difficult tumour cells to kill with conventional therapies, but hypoxia also promotes a more aggressive tumour phenotype. In the clinic, patients with primary tumours that contain large fractions of hypoxic cells have poor outcome, due in large part to limited treatment response and the presence of distant metastatic disease. My lab is interested in the role of tumour hypoxia (and the tumour microenvironment) in cancer therapy and in the development of tumour metastases.

Tumour Perfusion and Hypoxia

The extent of hypoxia in solid tumours can be measured by exogenous hypoxia markers (drugs that are bound and retained in hypoxic cells) and/or endogenous hypoxia markers (proteins that are increased in hypoxic cells). The oxygenation level of tumour cells can change as a function of time due to fluctuations in tumour perfusion, and this transient (or cyclic) hypoxia is poorly understood. We use positron emission tomography (PET), immunohistochemistry, and flow cytometry to quantify transiently hypoxic tumour cells with the goal of designing more effective therapeutic strategies to target (or exploit) tumour hypoxia. We also study the influence of ionizing radiation on tumour cell phenotype and invasion in models of breast and brain cancer.

Immune suppressive cells in solid tumour metastasis

The metastatic spread of cancer is associated with over 90% of cancer-related deaths. We have found that cytokines and other proteins secreted by tumours can stimulate the accumulation of immune modulatory cells in tissues prior to the arrival of metastatic tumour cells. Immune suppressive cells (e.g., myeloid-derived suppressor cells, macrophages, regulatory T cells) inhibit the cytotoxic function of effector T cells in several tissues, creating localized environments that allow metastasizing tumour cells to escape immune attack. Inhibition of immune suppressive cell recruitment and function leads to decreased metastatic tumour growth in the lungs, supporting therapeutic strategies to target immune suppressive cells in the clinic. We are also interested in how the immune system responds to tumour antigens and microenvironmental limitations to immune cell infiltration into solid tumours.

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