Photothermal therapy (PTT) is recently clinically established cancer therapy that uses near-infrared light for thermal ablation of solid tumors. The biopolymer N-dihydrogalactochitosan (GC) was shown in multiple reports to act as a very effective adjunct to tumor PTT. In the present study, mouse tumor model SCCVII (squamous cell carcinoma) was used with two protocols, in situ tumor PTT and therapeutic PTT vaccine for tumors, for investigating the effects of GC. The results reveal that GC can potentiate tumoricidal action of PTT through both direct and indirect mechanisms. In addition to previously known capacity of GC for activating immune effector cells, the indirect means is shown to include reducing the populations of immunoregulatory T cells (Tregs) in PTT-treated tumors. Testing the effects of GC on PTT-treated SCCVII tumor cells in vitro uncovered the existence of a direct mechanism evident by reduced colony survival of these cells. Fluorescence microscopy demonstrated increased binding of fluorescein-labeled GC to PTT-treated compared to untreated SCCVII cells that can be blocked by pre-exposure to annexin V. The results of additional in vitro testing with specific inhibitors demonstrate that these direct mechanisms do not involve the engagement of death surface receptors that trigger extrinsic apoptosis pathway signaling but may be linked to pro-survival activity of caspase-1. Based on the latter, it can be suggested that GC-promoted killing of PTT-treated cells stems from interference of GC bound to damaged membrane components with the repair of these structures that consequently hinders cell survival.

中文翻译：

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N-二氢半乳糖壳聚糖通过光热疗法和光热疗法产生的疫苗支持肿瘤控制。

光热疗法（PTT）是最近在临床上建立的一种癌症疗法，该疗法使用近红外光对实体瘤进行热消融。生物聚合物N-二氢半乳糖苷酶（GC）在多种报道中显示为肿瘤PTT的非常有效的辅助剂。在本研究中，将小鼠肿瘤模型SCCVII（鳞状细胞癌）与两种方案一起使用，即原位肿瘤PTT和用于肿瘤的治疗性PTT疫苗，以研究GC的作用。结果表明，GC可以通过直接和间接机制增强PTT的杀肿瘤作用。除了先前已知的GC激活免疫效应细胞的能力外，间接手段还显示出可以减少PTT治疗的肿瘤中免疫调节性T细胞（Tregs）的数量。在体外测试GC对PTT处理的SCCVII肿瘤细胞的作用后，发现了直接机制的存在，这些机制可通过降低这些细胞的集落存活率来证明。荧光显微镜证实，与未处理的SCCVII细胞相比，荧光素标记的GC与PTT处理的结合增加，可以通过预先暴露于膜联蛋白V来阻断。用特定抑制剂进行的其他体外测试结果表明，这些直接机制并不涉及死亡表面受体的参与触发外部细胞凋亡途径的信号传导，但可能与caspase-1的促生存活性有关。基于后者，可以建议GC促进对PTT处理的细胞的杀伤源于与受损膜成分结合的GC干扰这些结构的修复，从而阻碍了细胞存活。