Ogawa Mikako, Tomita Yusuke, Nakamura Yuko, Lee Min-Jung, Lee Sunmin, Tomita Saori, Nagaya Tadanobu, Sato Kazuhide, Yamauchi Toyohiko, Iwai Hidenao, Kumar Abhishek, Haystead Timothy, Shroff Hari, Choyke Peter L, Trepel Jane B, Kobayashi Hisataka
Medical Photonics Research Center, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
Laboratory for Bioanalysis and Molecular Imaging, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Oncotarget. 2017 Feb 7;8(6):10425-10436. doi: 10.18632/oncotarget.14425.
Immunogenic cell death (ICD) is a form of cell death that activates an adaptive immune response against dead-cell-associated antigens. Cancer cells killed via ICD can elicit antitumor immunity. ICD is efficiently induced by near-infrared photo-immunotherapy (NIR-PIT) that selectively kills target-cells on which antibody-photoabsorber conjugates bind and are activated by NIR light exposure. Advanced live cell microscopies showed that NIR-PIT caused rapid and irreversible damage to the cell membrane function leading to swelling and bursting, releasing intracellular components due to the influx of water into the cell. The process also induces relocation of ICD bio markers including calreticulin, Hsp70 and Hsp90 to the cell surface and the rapid release of immunogenic signals including ATP and HMGB1 followed by maturation of immature dendritic cells. Thus, NIR-PIT is a therapy that kills tumor cells by ICD, eliciting a host immune response against tumor.
免疫原性细胞死亡(ICD)是一种细胞死亡形式,可激活针对死细胞相关抗原的适应性免疫反应。通过ICD杀死的癌细胞可引发抗肿瘤免疫。近红外光免疫疗法(NIR-PIT)可有效诱导ICD,该疗法能选择性杀死抗体-光吸收剂偶联物结合并通过近红外光照射激活的靶细胞。先进的活细胞显微镜检查表明,NIR-PIT对细胞膜功能造成快速且不可逆的损伤,导致细胞肿胀和破裂,由于水流入细胞而释放细胞内成分。该过程还诱导包括钙网蛋白、热休克蛋白70(Hsp70)和热休克蛋白90(Hsp90)在内的ICD生物标志物重新定位到细胞表面,并快速释放包括三磷酸腺苷(ATP)和高迁移率族蛋白B1(HMGB1)在内的免疫原性信号,随后未成熟树突状细胞成熟。因此,NIR-PIT是一种通过ICD杀死肿瘤细胞、引发宿主针对肿瘤的免疫反应的疗法。