Immunogenic tumor cell death promotes dendritic cell migration and inhibits tumor growth via enhanced T cell immunity
Immunogenic tumor cell death enhances anti-tumor immunity. However, the mechanisms underlying this effect are incompletely understood. We established a system to induce tumor cell death in situ and investigated its effect on dendritic cell (DC) migration and T cell responses using intravital photolabeling in mice expressing KikGR photoconvertible protein. We demonstrate that tumor cell death induces phagocytosis of tumor cells by tumor-infiltrating (Ti)-DCs, and HMGB1-TLR4 and ATP-P2X7 receptor signaling-dependent Ti-DC emigration to draining lymph nodes (dLNs). This led to an increase in anti-tumor CD8(+) T cells of memory precursor effector phenotype and secondary tumor growth inhibition in a CD103(+) DC-dependent manner. However, combining tumor cell death induction with lipopolysaccharide treatment stimulated Ti-DC maturation and emigration to dLNs but did not improve tumor immunity. Thus, immunogenic tumor cell death enhances tumor immunity by increasing Ti-DC migration to dLNs where they promote anti-tumor T cell responses and tumor growth inhibition.
|Authors||Moriya, T. Kitagawa, K. Hayakawa, Y. Hemmi, H. Kaisho, T. Ueha, S. Ikebuchi, R. Yasuda, I. Nakanishi, Y. Honda, T. Matsushima, K. Kabashima, K. Ueda, M. Kusumoto, Y. Chtanova, T. Tomura, M.|
|Responsible Garvan Author||A/Prof Cecile King|