Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Cancer Immunol Res. 2017 Oct;5(10):832-838. doi: 10.1158/2326-6066.CIR-17-0055. Epub 2017 Aug 29.
Photodynamic therapy (PDT) is a clinically applied tumor ablation method that reduces tumor burden and may induce T-cell responses, providing a therapeutic option for mutated tumors. In this study, we applied PDT in two mouse tumor models and assessed its effect on outgrowth of PDT-treated and distant untreated tumors. PDT of established tumors resulted in complete tumor eradication in most mice, which were then protected against tumor rechallenge. Correspondingly, the therapeutic effect was abrogated upon systemic depletion of CD8 T cells, indicating PDT-induced tumor antigen cross-presentation and T-cell activation. In a double-tumor model, PDT of primary tumors induced enhanced infiltration of untreated distant tumors by CD8 T cells, which significantly delayed their outgrowth. Combination therapy of PDT and CTLA-4-blocking antibodies significantly improved therapeutic efficacy and survival of double-tumor-bearing mice. These results show that local tumor ablation by PDT induces CD8 T-cell responses crucial for systemic tumor eradication, which can be further enhanced by combination with immune checkpoint blockade. This combination of two clinically applied therapies may be a treatment strategy for advanced cancer without previous knowledge of tumor-specific antigens. .
光动力疗法（PDT）是一种临床应用的肿瘤消融方法，可减轻肿瘤负担，并可能诱导 T 细胞反应，为突变肿瘤提供治疗选择。在这项研究中，我们将 PDT 应用于两种小鼠肿瘤模型，并评估其对 PDT 治疗的肿瘤和远处未治疗肿瘤生长的影响。在大多数小鼠中，PDT 治疗已建立的肿瘤导致完全消除肿瘤，这些小鼠随后受到肿瘤再挑战的保护。相应地，在系统性耗尽 CD8 T 细胞后，治疗效果被消除，表明 PDT 诱导的肿瘤抗原交叉呈递和 T 细胞激活。在双肿瘤模型中，PDT 治疗原发性肿瘤诱导未治疗的远处肿瘤中 CD8 T 细胞的浸润增强，显著延缓其生长。PDT 和 CTLA-4 阻断抗体的联合治疗显著提高了双肿瘤荷瘤小鼠的治疗效果和生存率。这些结果表明，PDT 引起的局部肿瘤消融诱导了对系统性肿瘤消除至关重要的 CD8 T 细胞反应，通过与免疫检查点阻断联合使用可以进一步增强这种反应。这两种临床应用疗法的联合可能是一种治疗方法，适用于以前不知道肿瘤特异性抗原的晚期癌症。
