Immunogenic cancer cell death selectively induced by near infrared photoimmunotherapy initiates host tumor immunity.

Immunogenic cancer cell death selectively induced by near infrared photoimmunotherapy initiates host tumor immunity.
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DOI:
10.18632/oncotarget.14425
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发表时间:
2017-02-07
期刊:
影响因子:
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通讯作者:
Kobayashi H
Kobayashi H
中科院分区:
其他
文献类型:
--
作者:
Ogawa M;Tomita Y;Nakamura Y;Lee MJ;Lee S;Tomita S;Nagaya T;Sato K;Yamauchi T;Iwai H;Kumar A;Haystead T;Shroff H;Choyke PL;Trepel JB;Kobayashi H

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免疫原性细胞死亡(ICD)是细胞死亡的一种形式,它激活对死细胞相关抗原的适应性免疫反应。通过ICD杀死的癌细胞可引起抗肿瘤免疫。ICD是由近红外光免疫疗法(NIR- pit)有效诱导的,该疗法选择性地杀死抗体-光吸收剂结合的靶细胞,并被近红外光照射激活。先进的活细胞显微镜显示,NIR-PIT对细胞膜功能造成快速和不可逆的损害,导致肿胀和破裂,由于水流入细胞而释放胞内成分。该过程还诱导ICD生物标志物钙网蛋白、Hsp70和Hsp90向细胞表面迁移,并快速释放包括ATP和HMGB1在内的免疫原性信号,随后使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,引发宿主对肿瘤的免疫反应的疗法。
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.