Laboratory of Immunology, Faculty of Pharmacy, Osaka Ohtani University, Tondabayashi, Osaka, 584-8540, Japan.
Laboratory of Veterinary Physiology, Department of Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, 069-8501, Japan.
Cancer Immunol Immunother. 2022 Dec;71(12):3099-3106. doi: 10.1007/s00262-022-03216-2. Epub 2022 May 28.
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 CD326 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.
近红外光免疫治疗(NIR-PIT)选择性地杀死与光吸收染料 IR700DX 结合的抗体结合的肿瘤细胞,并诱导全身性抗肿瘤免疫反应。NIR-PIT 诱导免疫原性细胞死亡(ICD),从死亡的肿瘤细胞中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 是否会影响浸润肿瘤的(Ti)-DC 向引流淋巴结(dLNs)的迁移,在那里诱导全身性抗肿瘤反应。在这里,我们利用可光转化蛋白 Kikume Green-Red(KikGR)小鼠肿瘤中 Ti-DC 的体内光标记,表明 NIR-PIT 增强了包括 cDC1s、cDC2s 和 CD326 DC 在内的 Ti-DC 向 dLNs 的迁移。这种作用被阻断三磷酸腺苷(ATP)所消除,ATP 是 DAMPs 分子之一,以及通过百日咳毒素抑制 Gαi 信号转导。因此,NIR-PIT 通过 ATP-P2X7 受体和 Gαi 蛋白偶联受体信号通路诱导 ICD,刺激 Ti-DC 向 dLNs 的迁移,并可能增强肿瘤抗原呈递,在 dLNs 中诱导抗肿瘤 T 细胞。
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