High fluence low-level laser (HF-LLL), a mitochondria-targeted tumour phototherapy, results in oxidative damage and apoptosis of tumour cells, as well as damage to normal tissue. To circumvent this, the therapeutic effect of low fluence LLL (LFL), a non-invasive and drug-free therapeutic strategy, was identified for tumours and the underlying molecular mechanisms were investigated. We observed that LFL enhanced antigen-specific immune response of macrophages and dendritic cells by upregulating MHC class II, which was induced by mitochondrial reactive oxygen species (ROS)-activated signalling, suppressing tumour growth in both CD11c-DTR and C57BL/6 mice. Mechanistically, LFL upregulated MHC class II in an MHC class II transactivator (CIITA)-dependent manner. LFL-activated protein kinase C (PKC) promoted the nuclear translocation of CIITA, as inhibition of PKC attenuated the DNA-binding efficiency of CIITA to MHC class II promoter. CIITA mRNA and protein expression also improved after LFL treatment, characterised by direct binding of Src and STAT1, and subsequent activation of STAT1. Notably, scavenging of ROS downregulated LFL-induced Src and PKC activation and antagonised the effects of LFL treatment. Thus, LFL treatment altered the adaptive immune response via the mitochondrial ROS-activated signalling pathway to control the progress of neoplastic disease.

高能量低能激光（HF-LLL）是一种靶向线粒体的肿瘤光疗，会导致肿瘤细胞的氧化损伤和凋亡，以及对正常组织的损伤。为了避免这种情况，确定了低能量 LLL (LFL) 的治疗效果，这是一种非侵入性和无药物治疗策略，对肿瘤的治疗效果进行了研究，并研究了潜在的分子机制。我们观察到 LFL 通过上调由线粒体活性氧 (ROS) 激活的信号传导诱导的 MHC II 类增强巨噬细胞和树突状细胞的抗原特异性免疫反应，抑制 CD11c-DTR 和 C57BL/6 小鼠的肿瘤生长。从机制上讲，LFL 以 MHC II 类反式激活因子 (CIITA) 依赖的方式上调 MHC II 类。LFL活化的蛋白激酶C（PKC）促进CIITA的核转位，由于 PKC 的抑制减弱了 CIITA 与 MHC II 类启动子的 DNA 结合效率。LFL 处理后 CIITA mRNA 和蛋白质表达也有所改善，其特征是 Src 和 STAT1 的直接结合，以及随后的 STAT1 激活。值得注意的是，清除 ROS 可下调 LFL 诱导的 Src 和 PKC 活化并拮抗 LFL 治疗的效果。因此，LFL 治疗改变了适应性免疫反应通过线粒体 ROS 激活的信号通路来控制肿瘤疾病的进展。