Immunoregulatory cytokines that are important in breast and prostate cancer metastasis

bone metOne focus of our lab is to understand immune responses during cancer, with a particular interest in the crosstalk between cancer cells and immune cells that regulate metastatic spread. We have already established that tumours cell secrete immunostimulatory cytokines such as type I interferons and that loss of these signals is important in metastatic progression in breast cancer. Our current focus is to dissect tissue-specific immune responses (including immune landscape using multiplex IHC as pictured, top image), immunoregulatory cytokines (such as IFNs) and checkpoint proteins (such as the PDL1/PDL1 axis) that have important roles in metastatic progression in breast and prostate cancer and to use this information to design new prognostic markers and therapeutic strategies for metastatic disease.

A particular interest of the laboratory is bone metastasis, and projects in the laboratory aim to study the bone specific immune-milieu and how it is altered during bone metastatic cancer, including the role of immunity in keeping cancer cells in a dormant state. This includes identification of tumour-induced alterations in immunostimulatory and suppressive cytokines, and immune effector and suppressor cells that are involved in this process.  Utilising a bone-metastatic model of prostate cancer (bone metastases pictured, bottom image), we have recently optimized a technique to identify and isolate dormant prostate cancer cells from bone. As part of the PROMIS team (funded by the PCFA/Movember), transcriptional profiles of these dormant cells have been generated and key pathways have been identified that are altered during outgrowth from dormancy. These pathways are currently being validated for their prognostic, mechanistic and therapeutic implications.