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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.

Type Journal
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
Publisher Name iScience
Published Date 2021-04-14
Published Volume 24
Published Issue 5
Published Pages 102424
Status Always Electronic
DOI 10.1016/j.isci.2021.102424