[Truncated abstract] Chemotherapy and immunotherapy have historically been considered antagonistic treatment options due to the variable lymphopaenia experienced as a side effect of most cytotoxic drugs. Recently, research in animal models has demonstrated that chemotherapy may actually enhance the generation of anti-tumour immunity through altering both the level and context of antigen presentation. However, despite increasing interest in combining chemo and immunotherapy for the treatment of cancer, little is known of the effects of chemotherapy on the anti-tumour immune response in humans. This study investigated the longitudinal effects of chemotherapy on T cell subsets over four treatment cycles in a cohort of patients with malignant mesothelioma (MM) and non-small cell lung cancer (NSCLC) using multi-parameter flow cytometry. At baseline, patients had higher proportions of proliferating and activated effector CD8+ T cells and a larger regulatory T cell (Treg) population than healthy controls, consistent with the presence of an underlying anti-tumour immune response. Total lymphocyte numbers were significantly reduced one week following the first dose of chemotherapy and then continued to decline at a slower rate throughout the course of treatment. Proliferating CD8+ T cells, CD4+ T cells and Treg were almost entirely depleted, but rapidly recovered with higher than baseline levels of proliferating cells at the end of each treatment cycle as the T cell pool regenerated. Treg were most profoundly affected, with a decline in the relative size of the population one week after chemotherapy, but a more pronounced rebound in proliferating cells at the end of each cycle. No differences were observed between patients with MM and those with NSCLC.
|Qualification||Doctor of Philosophy|
|Publication status||Unpublished - 2011|