Department of Neurosurgery, The Second Affiliated Hospital, Sun Yat-Sen University, No. 107 West Road of Riverside, Guangzhou, 510120, China.
J Neurooncol. 2011 Nov;105(2):199-210. doi: 10.1007/s11060-011-0584-7. Epub 2011 Apr 26.
Numerous studies have established that photodynamic therapy (PDT) can trigger tumor-specific immunity and cancer cell immunogenicity, both of which play a critical role in the long-term control of oncogenesis; however, the underlying mechanisms are largely unexplained. Deficiency of the transporter associated with antigen processing 1 (TAP1) has been observed in a variety of tumors, and the question has been raised whether the restoration of TAP1 could facilitate the activation of antitumor immunity. To elucidate the mechanisms underlying PDT-induced immunopotentiation, we examined the hypothesis that upregulating TAP1 via PDT may contribute to enhancement of antitumor immunity and cancer cell immunogenicity. In this study, we investigated the effects of PDT on the expression and function of TAP1 in glioma cells. We found that HMME-based PDT restored TAP1 expression in a rapid and transient manner. Furthermore, the newly synthesized TAP1 protein was capable of potentiating the activity of transporting antigen peptides. As a result, restoration of the expression and function of TAP1 translated into augmenting the presentation of surface MHC class I molecules. Overall, our data indicate that PDT enables glioma cells to recover both the expression of functional TAP1 and the presentation of surface MHC class I antigens, which are processes that may enhance antitumor immunity after PDT. These findings may have implications for PDT and provide new insights into the mechanisms underlying PDT-induced immunopotentiation.
大量研究已经证实,光动力疗法(PDT)可以触发肿瘤特异性免疫和癌细胞免疫原性,这两者在肿瘤长期控制中都起着至关重要的作用;然而,其潜在机制在很大程度上仍未得到解释。在各种肿瘤中都观察到抗原加工相关转运体 1(TAP1)的缺失,并且有人提出是否可以通过恢复 TAP1 来促进抗肿瘤免疫的激活。为了阐明 PDT 诱导免疫增强的机制,我们检验了这样一个假设,即通过 PDT 上调 TAP1 可能有助于增强抗肿瘤免疫和癌细胞免疫原性。在这项研究中,我们研究了 PDT 对神经胶质瘤细胞中 TAP1 表达和功能的影响。我们发现,基于 HMME 的 PDT 可快速且短暂地恢复 TAP1 表达。此外,新合成的 TAP1 蛋白能够增强转运抗原肽的活性。结果,TAP1 的表达和功能的恢复转化为增强表面 MHC I 类分子的呈递。总的来说,我们的数据表明,PDT 使神经胶质瘤细胞能够恢复功能性 TAP1 的表达和表面 MHC I 类抗原的呈递,这些过程可能会增强 PDT 后的抗肿瘤免疫。这些发现可能对 PDT 具有重要意义,并为 PDT 诱导免疫增强的机制提供了新的见解。