Hypericin-based photodynamic therapy induces surface exposure of damage-associated molecular patterns like HSP70 and calreticulin
Hypericin-based photodynamic therapy induces surface exposure of damage-associated molecular patterns like HSP70 and calreticulin
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DOI：
10.1007/s00262-011-1184-2
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发表时间：
2012-02-01
影响因子：
5.8
通讯作者：
Agostinis, Patrizia
中科院分区：
文献类型：
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作者：
Garg, Abhishek D.;Krysko, Dmitri V.;Agostinis, Patrizia
表面暴露的HSP70和钙网蛋白是损伤相关的分子模式(DAMP)，对调节癌症治疗的成功至关重要。光动力疗法(PDT)包括给药一种光敏剂(PTS)，然后进行可见光照射。由此产生的活性氧通过破坏肿瘤的微血管系统并引发局部炎症反应直接杀死肿瘤。伴有PTS PHOTOFRIN的PDT与湿气暴露有关，但对于其他PTS则不是这样。在这里，我们展示了当癌细胞被基于金丝桃素的光动力疗法(Hyp-PDT)处理时，它们表面暴露了HSP70和钙网蛋白(CRT)。CRT暴露的诱导并不伴随ERp57的共同暴露，但这并不影响暴露的CRT调节树突状细胞吞噬Hyp-PDT治疗的癌细胞的能力。有趣的是，我们发现Hyp-PDT诱导的CRT暴露(与蒽环类药物诱导的CRT暴露相反)与ERp57的存在无关。我们的结果表明，Hyp-PDT是一种潜在的抗癌免疫原性药物。
Surface-exposed HSP70 and calreticulin are damage-associated molecular patterns (DAMPs) crucially involved in modulating the success of cancer therapy. Photodynamic therapy (PDT) involves the administration of a photosensitising (PTS) agent followed by visible light-irradiation. The reactive oxygen species that are thus generated directly kill tumours by damaging their microvasculature and inducing a local inflammatory reaction. PDT with the PTS photofrin is associated with DAMPs exposure, but the same is not true for other PTSs. Here, we show that when cancer cells are treated with hypericin-based PDT (Hyp-PDT), they surface-expose both HSP70 and calreticulin (CRT). Induction of CRT exposure was not accompanied by co-exposure of ERp57, but this did not compromise the ability of the exposed CRT to regulate the phagocytosis of Hyp-PDT-treated cancer cells by dendritic cells. Interestingly, we found that Hyp-PDT-induced CRT exposure (in contrast to anthracycline-induced CRT exposure) was independent of the presence of ERp57. Our results indicate that Hyp-PDT is a potential anti-cancer immunogenic modality.