文章：

光热治疗诱导的免疫原性细胞死亡协同增强免疫检查点抑制剂的治疗效果

Photothermal Therapy-Induced Immunogenic Cell Death Synergistically Enhances the Therapeutic Effect of Immune Checkpoint Inhibitors

原文发布日期：16 January 2026

DOI: 10.3390/cancers18020287

类型: Article

开放获取: 是

英文摘要：

Background/Objectives:To improve the response rate of immune checkpoint inhibitors (ICIs), inducing immunogenic cell death (ICD) is a promising approach. Photothermal therapy (PTT) induces immunogenic cell death and activates anti-tumor immunity. While there are various ICD inducers, the difference in ICD induction by various modalities is poorly understood. In this study, we found previously unrecognized advantages of PTT compared to anti-cancer drugs and showed the usefulness of PTT as an anti-cancer drug-free approach to be combined with immunotherapy.Methods:Gold nanorods were synthesized as photothermal agents and added to culture medium or locally administered to tumor tissues. Mitoxantrone (MIT), an ICD inducer, and cisplatin (CDDP), a non-ICD inducer, were compared with PTT. To assess the induction of ICD, the subcellular localization and amounts of high mobility group box 1 (HMGB1) and calreticulin (CRT) were observed using immunofluorescent staining. FM3A tumor-bearing mice were treated with PTT or anti-cancer drugs, and cell death and DAMPs localization in tumor tissues were analyzed. Also, the supra-additive effect of PTT on ICI was observed. Tumor-infiltrating CD8+T cells were examined to evaluate the immune status in tumor tissues.Results:In vivo assays showed that PTT induces HMGB1 release and increased expression of CRT on the cell membrane. Moreover, PTT showed a supra-additive effect in terms of therapeutic effect and anti-tumor activation when combined with an immune checkpoint inhibitor.Conclusions:In this study, we demonstrated that PTT induced ICD-related signaling and improved the response rate of ICI, which means PTT is a promising combination therapy with ICI.

摘要翻译： 

背景/目的： 为提高免疫检查点抑制剂（ICIs）的应答率，诱导免疫原性细胞死亡（ICD）是一种有前景的方法。光热疗法（PTT）可诱导免疫原性细胞死亡并激活抗肿瘤免疫。尽管存在多种ICD诱导剂，但不同方式诱导ICD的差异尚不清楚。在本研究中，我们发现与抗癌药物相比，PTT具有先前未被认识到的优势，并展示了PTT作为一种无需抗癌药物、可与免疫疗法联合使用的策略的实用性。

方法： 合成了金纳米棒作为光热剂，将其加入培养基或局部注射至肿瘤组织。将一种ICD诱导剂米托蒽醌（MIT）和非ICD诱导剂顺铂（CDDP）与PTT进行比较。为评估ICD的诱导情况，采用免疫荧光染色观察高迁移率族蛋白B1（HMGB1）和钙网蛋白（CRT）的亚细胞定位及表达量。对携带FM3A肿瘤的小鼠进行PTT或抗癌药物治疗，分析肿瘤组织中的细胞死亡及损伤相关分子模式（DAMPs）的定位。同时，观察了PTT对ICI的协同增强效应。通过检测肿瘤浸润性CD8⁺ T细胞评估肿瘤组织内的免疫状态。

结果： 体内实验表明，PTT诱导了HMGB1的释放并增加了细胞膜上CRT的表达。此外，当与免疫检查点抑制剂联合使用时，PTT在治疗效果和抗肿瘤激活方面表现出协同增强效应。

结论： 本研究表明，PTT诱导了ICD相关信号传导，并提高了ICI的应答率，这意味着PTT是一种与ICI联合治疗的有前景的疗法。

原文链接：

Photothermal Therapy-Induced Immunogenic Cell Death Synergistically Enhances the Therapeutic Effect of Immune Checkpoint Inhibitors