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.
|ISBN||2589-0042 (Electronic) 2589-0042 (Linking)|
|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|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/33997702|