T Cell Therapy of Breast Cancer; Challenges and Opportunities

T cell therapy is a promising approach in cancer treatment that aims to use the body’s own immune system to rid itself of cancer. The therapy involves isolating T cells that react to the tumour from a patient’s blood, expanding their numbers in culture and infusing them back into the patient, with the expectation that the T cells will recognize and destroy cancer cells throughout the body. This approach has yet to be applied clinically to breast cancer. MSFHR funded Michele Martin’s early PhD work using an innovative mouse mammary tumour model to study this approach for future use in human breast cancer. By infusing tumour-reactive T cells, she has been able to induce complete tumour regression of about 37 per cent of tumours, an unprecedented result compared to other forms of immunotherapy. However, the remaining tumours show partial regression or no regression at all. Martin now seeks to understand why some tumours are resistant to this treatment. Intriguingly, while all regressing tumours demonstrate heavy infiltration with T cells after treatment, many non-regressing tumours show no infiltration at all. Martin’s hypothesis is that many resistant tumours are able to physically exclude T cells. Her research will determine the molecular factors behind the physical mechanisms contributing to a tumour's exclusion of these T cells, and test whether she can disrupt the tumour environment to facilitate the effective infiltration of T cells. The information gathered from Martin’s genetic analysis of infiltrated and uninfiltrated/resistant tumours will provide valuable data for defining the molecular barriers to T cell infiltration, and could point to ways to overcome these barriers.