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
Affiliations
Taiki Moriya
Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka 584-8540, Japan
Kurumi Kitagawa
Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka 584-8540, Japan
Yuuki Hayakawa
Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka 584-8540, Japan
Hiroaki Hemmi
Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Graduate school of Medicine, Wakayama, Wakayama 641-8509, Japan
Tsuneyasu Kaisho
Department of Immunology, Institute of Advanced Medicine, Wakayama Medical University, Graduate school of Medicine, Wakayama, Wakayama 641-8509, Japan
Satoshi Ueha
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda City Chiba 278-0022, Japan
Ryoyo Ikebuchi
Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka 584-8540, Japan; Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan
Ippei Yasuda
Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka 584-8540, Japan
Yasutaka Nakanishi
Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka 584-8540, Japan
Tetsuya Honda
Department of Dermatology, Kyoto University, Graduate School of Medicine, Sakyou-ku, Kyoto 606-8507, Japan
Koji Matsushima
Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda City Chiba 278-0022, Japan
Kenji Kabashima
Department of Dermatology, Kyoto University, Graduate School of Medicine, Sakyou-ku, Kyoto 606-8507, Japan
Mizuki Ueda
Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka 584-8540, Japan
Yutaka Kusumoto
Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka 584-8540, Japan
Tatyana Chtanova
Immunology Theme, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales Sydney, Kensington, NSW 2033 Australia
Michio Tomura
Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka 584-8540, Japan; Corresponding author
Summary: 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.
