title: HMME-based PDT restores expression and function of transporter associated with antigen processing 1 (TAP1) and surface presentation of MHC class I antigen in human glioma.
abstract: 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.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, Sun Yat-Sen University, No. 107 West Road of Riverside, Guangzhou, 510120, China.
authors.forename: Shan-Yi
authors.initials: SY
authors.lastname: Zhang
authors.forename: Jun-Liang
authors.initials: JL
authors.lastname: Li
authors.forename: Xin-Ke
authors.initials: XK
authors.lastname: Xu
authors.forename: Mei-Guang
authors.initials: MG
authors.lastname: Zheng
authors.forename: Cheng-Cai
authors.initials: CC
authors.lastname: Wen
authors.forename: Fang-Cheng
authors.initials: FC
authors.lastname: Li
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D017951:Antigen Presentation; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D049109:Cell Proliferation; D002470:Cell Survival; D005434:Flow Cytometry; D005910:Glioma / Q000276:immunology* / Q000378:metabolism* / Q000628:therapy; D006415:Hematoporphyrins / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma; D010778:Photochemotherapy; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D006415:Hematoporphyrins; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C073119:TAP1 protein, human; C494379:hematoporphyrin monomethyl ether; D007371:Interferon-gamma