Adoptive cell therapy (ACT) is a strategy to treat cancer. However, not all ACT trials are successful because of several factors. In the case of ACT using cytotoxic T lymphocytes (CTLs), T cell dysfunction is one of the most significant causes of failure. Our group reported that CTLs used for ACT against the mouse Eμ-myc lymphoma model are deleted or inactivated in an antigen-specific fashion upon encounter of large tumour cell burdens. The mechanism of T cell inactivation, which we named “stunning”, takes place within 24 hours after ACT. We hypothesize stunning is triggered by simultaneous or frequent interactions between CTL and tumour cells, and occurs independently of TCR affinity to antigen or the expression level of antigen per cell [1][2][3].
As the density of tumour cells that interact with CTLs is a critical inducer of stunning, analyzing how tumour grows in organs may provide clues to understand how CTL reach and interact with tumour cells, and perhaps how the geometry of this interaction causes stunning. We hypothesize that If tumour aggregates more in a particular area, tumour infiltrating CTL would have multiple contacts with tumour cells in a short period, which may easily lead to stunning. On the other hand, if tumour cells widely spread and form smaller mass, there will be less multiple tumour-CTL interaction. By using confocal microscopy, I will investigate localization and structure of Eμ-myc lymphoma cells in spleen and lymph nodes. The stunning phenomena has been described mainly in spleen but lymphoma cells and CTLs also can migrate to other organs. Therefore, other organs including non-lymphoid organs also will be investigated.