Immunogenic tumor cell death promotes dendritic cell migration and inhibits tumor growth via enhanced T cell immunity

Taiki Moriya; Kurumi Kitagawa; Yuuki Hayakawa; Hiroaki Hemmi; Tsuneyasu Kaisho; Satoshi Ueha; Ryoyo Ikebuchi; Ippei Yasuda; Yasutaka Nakanishi; Tetsuya Honda; Koji Matsushima; Kenji Kabashima; Mizuki Ueda; Yutaka Kusumoto; Tatyana Chtanova; Michio Tomura

doi:10.1016/j.isci.2021.102424

Immunogenic tumor cell death promotes dendritic cell migration and inhibits tumor growth via enhanced T cell immunity

iScience. 2021 Apr 14;24(5):102424. doi: 10.1016/j.isci.2021.102424. eCollection 2021 May 21.

Authors

Taiki Moriya¹, Kurumi Kitagawa¹, Yuuki Hayakawa¹, Hiroaki Hemmi², Tsuneyasu Kaisho², Satoshi Ueha³, Ryoyo Ikebuchi^{1

4}, Ippei Yasuda¹, Yasutaka Nakanishi¹, Tetsuya Honda⁵, Koji Matsushima³, Kenji Kabashima⁵, Mizuki Ueda¹, Yutaka Kusumoto¹, Tatyana Chtanova^{6

7}, Michio Tomura¹

Affiliations

¹ Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka 584-8540, Japan.
² Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Graduate school of Medicine, Wakayama, Wakayama 641-8509, Japan.
³ Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda City Chiba 278-0022, Japan.
⁴ Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan.
⁵ Department of Dermatology, Kyoto University, Graduate School of Medicine, Sakyou-ku, Kyoto 606-8507, Japan.
⁶ Immunology Theme, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
⁷ School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales Sydney, Kensington, NSW 2033 Australia.

Abstract

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.

Keywords: Cancer; Cell Biology; Immunology.