The fate of tumour-egressing T cells in tumour immune responses

Tumour-infiltrating T cells are a key component of the tumour microenvironment and their presence within the tumour can dramatically alter anti-tumour responses. While some immune cells, such as CD8+ T cells, can have an anti-tumour role and destroy tumour cells, others, such as regulatory T cells (Treg cells), play a pro-tumour role and promote tumour growth by impairing anti-tumour immunity. Despite their impact on tumour growth, the fate of tumour-infiltrating cells is largely unknown. In this thesis it has been hypothesised that tumour-infiltrating cells leave primary tumour deposits and play a key role in tumour immunity in draining lymph nodes.Using Kaede photoconvertible mice a method has been developed to label and track tumour-infiltrating cells, demonstrating that these cells leave primary tumours and accumulate in draining lymph node. Flow cytometric analysis revealed that the largest tumour-egressing population in draining lymph nodes was represented by T cells, of which 80% are antigen-experienced. While Treg cells represented a minor fraction of the migratory population, γδ T cell proportions were substantially enriched. Compared to total lymph node T cells, tumour-egressing T cells showed enhanced effector functions: γδ T cells showed increased IL-17A+ and decreased IFN-γ+ proportions, whereas αβ CD4+ and CD8+ T cells had enriched IFN-γ+ proportions and expressed increased cytotoxicity marker CD107a. Moreover, tumour-conditioned T cell migration to draining lymph nodes involved G protein-coupled receptors but occurred independently of CCR7 or CD62L.In summary, it has been demonstrated for the first time that tumour-infiltrating T cells leave tumour sites and migrate to the draining lymph node to perform effector functions that may modulate anti-tumour immune responses. Collectively, these results provide insights into the role of tumour-conditioned T cells that could have important implications for the design of T-cell based anti-tumour immune therapies