Targeting Immunological Restrainers: Understanding the Immunology Behind Combination Chemoimmunotherapy to Improve the Treatment of Malignant Mesothelioma.

摘要

This FINAL report summarizes all worked completed to date with respect to all Aims listed in the original proposal and highlights key research discoveries. This study investigated the role the body's immune system plays during mesothelioma tumour development with a specific focus on a subset of immune cells called Treg that act to limit anti-tumour immunity. We demonstrate that previously published inhibitors of Treg cells are not effective in our models. However, we employed a new animal model which allows for the selective depletion of Treg cells and observed that targeted removal of Treg, particularly during early tumour development can significantly enhance anti-tumour immunity and delay tumour development. Importantly targeted Treg removal in combination with gemcitabine chemotherapy significantly enhanced overall survival in comparison to chemotherapy alone. .Additionally, we observed that asbestos induced mesothelioma development is slower in mice that lack a functional immune system compared to mice that are immune competent. We have developed a number of cell lines that will enable further investigation into the role of the host immune system during the induction of asbestos induced mesothelioma and disease progression. Data generated from this work underpins our focus on developing immunotherapies for improved treatment of malignant mesothelioma.