Near-infrared photoimmunotherapy induced tumor cell death enhances tumor dendritic cell migration.

Near-infrared photoimmunotherapy induced tumor cell death enhances tumor dendritic cell migration.
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DOI:
10.1007/s00262-022-03216-2
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发表时间:
2022-12
影响因子:
5.8
通讯作者:
Tomura, Michio
Tomura, Michio
中科院分区:
医学3区
文献类型:
--
作者:
Moriya, Taiki;Hashimoto, Mayuko;Matsushita, Hina;Masuyama, Shion;Yoshida, Rina;Okada, Ryuhei;Furusawa, Aki;Fujimura, Daiki;Wakiyama, Hiroaki;Kato, Takuya;Choyke, Peter L.;Kusumoto, Yutaka;Chtanova, Tatyana;Kobayashi, Hisataka;Tomura, Michio

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近红外光免疫疗法(NIR-PIT)选择性地杀死与光吸收剂染料IR 700DX缀合的抗体结合的肿瘤细胞,并诱导全身性抗肿瘤免疫应答。NIR-PIT诱导免疫原性细胞死亡(ICD),从垂死的肿瘤细胞释放损伤相关分子模式(DAMP)分子,并激活树突状细胞(DC)。然而,目前尚不清楚NIR-PIT是否影响肿瘤浸润性(Ti)-DC向引流淋巴结(dLN)的迁移,其中诱导全身性抗肿瘤应答。在此,我们利用光转化蛋白KikGR绿红(KikGR)小鼠中肿瘤中Ti-DC的体内光标记来显示NIR-PIT增强Ti-DC(包括cDC 1、cDC 2和CD 326 + DC)向dLN的迁移。阻断DAMP分子之一的三磷酸腺苷(ATP)以及百日咳毒素抑制Gαi信号传导可消除这种效应。因此,通过NIR-PIT的ICD诱导通过ATP-P2 X7受体和Gαi蛋白偶联受体信号传导途径刺激Ti-DC向dLN的迁移,并且可以增强肿瘤抗原呈递以诱导dLN中的抗肿瘤T细胞。
Near-infrared photoimmunotherapy (NIR-PIT) selectively kills tumor cells to which the photo-absorber dye IR700DX-conjugated antibodies are bound and induces a systemic anti-tumor immune response. NIR-PIT induces immunogenic cell death (ICD), releases damage-associated molecular patterns (DAMPs) molecules from dying tumor cells, and activates dendritic cells (DCs). However, it is unclear whether NIR-PIT affects migration of tumor-infiltrating (Ti)-DCs to draining lymph nodes (dLNs), where a systemic anti-tumor response is induced. Here, we utilized in vivo photolabeling of Ti-DCs in tumors in photoconvertible protein Kikume Green-Red (KikGR) mice to show that NIR-PIT enhanced migration of Ti-DCs including cDC1s, cDC2s, and C D326+ DCs to dLNs. This effect was abolished by blocking adenosine triphosphate (ATP), one of the DAMPs molecules, as well as by inhibition of Gαi signaling by pertussis toxin. Thus, ICD induction by NIR-PIT stimulates Ti-DC migration to dLNs via ATP-P2X7 receptor and Gαi protein-coupled receptor signaling pathways and may augment tumor antigen presentation to induce anti-tumor T cells in dLNs.
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