Sasaki Makiko, Tanaka Mamoru, Kojima Yuki, Nishie Hirotada, Shimura Takaya, Kubota Eiji, Kataoka Hiromi
Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Science, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan.
Mol Ther Oncolytics. 2023 Jan 2;28:118-131. doi: 10.1016/j.omto.2022.12.009. eCollection 2023 Mar 16.
Photodynamic therapy (PDT) is a relatively non-invasive anti-cancer therapy that employs a photosensitizer with a specific wavelength of light irradiation. PDT induces direct cell killing and enhancement effects on tumor immunity, but its underlying mechanism remains unknown. Here, we perform a basic analysis of the anti-tumor effect of talaporfin sodium (TS)-PDT as well as its synergism with the immune checkpoint inhibitor anti-programmed death 1 (anti-PD-1) antibody. We estimate the cell death mechanism induced by TS-PDT and the induction of damage-associated molecular patterns (DAMPs) by TS-PDT . We establish a syngeneic mouse model of bilateral flank tumors and verify the enhancement of the abscopal effect on the non-irradiated side. TS-PDT induced apoptosis, necrosis, and autophagy-associated cell death . TS-PDT induced the release and/or expression of DAMPs . Tumor growth was inhibited in the TS-PDT and anti-PD-1 antibody combination group compared with other single-treatment or non-treatment groups . In summary, TS-PDT induces the release and/or expression of DAMPs, indicating that it activates innate immunity. PD-1 blockage enhances the anti-tumor immunity induced by TS-PDT. Thus, our results demonstrate that the combination of TS-PDT and anti-PD-1 antibody can potentially be used for anti-tumor therapy.
光动力疗法(PDT)是一种相对非侵入性的抗癌疗法,它使用一种光敏剂并结合特定波长的光照射。PDT可诱导直接的细胞杀伤作用并增强肿瘤免疫效应,但其潜在机制尚不清楚。在此,我们对他拉泊芬钠(TS)-PDT的抗肿瘤作用及其与免疫检查点抑制剂抗程序性死亡蛋白1(抗PD-1)抗体的协同作用进行了基础分析。我们评估了TS-PDT诱导的细胞死亡机制以及TS-PDT对损伤相关分子模式(DAMPs)的诱导作用。我们建立了双侧胁腹肿瘤的同基因小鼠模型,并验证了对未照射侧的远隔效应增强情况。TS-PDT诱导了凋亡、坏死和自噬相关的细胞死亡。TS-PDT诱导了DAMPs的释放和/或表达。与其他单药治疗或未治疗组相比,TS-PDT与抗PD-1抗体联合治疗组的肿瘤生长受到抑制。总之,TS-PDT诱导了DAMPs的释放和/或表达,表明它激活了固有免疫。阻断PD-1可增强TS-PDT诱导的抗肿瘤免疫。因此,我们的结果表明,TS-PDT与抗PD-1抗体联合使用可能具有抗肿瘤治疗潜力。