title: Phototherapy-Induced Antitumor Immunity: Long-Term Tumor Suppression Effects via Photoinactivation of Respiratory Chain Oxidase-Triggered Superoxide Anion Burst.
abstract: OBJECTIVE
  Our previous studies have demonstrated that as a mitochondria-targeting cancer phototherapy, high-fluence, low-power laser irradiation (HF-LPLI) results in oxidative damage that induces tumor cell apoptosis. In this study, we focused on the immunological effects of HF-LPLI phototherapy and explored its antitumor immune regulatory mechanism.
  
  
  RESULTS
  We found not only that HF-LPLI treatment induced tumor cell apoptosis but also that HF-LPLI-treated apoptotic tumor cells activated macrophages. Due to mitochondrial superoxide anion burst after HF-LPLI treatment, tumor cells displayed a high level of phosphatidylserine oxidation, which mediated the recognition and uptake by macrophages with the subsequent secretion of cytokines and generation of cytotoxic T lymphocytes. In addition, in vivo results showed that HF-LPLI treatment caused leukocyte infiltration into the tumor and efficaciously inhibited tumor growth in an EMT6 tumor model. These phenomena were absent in the respiration-deficient EMT6 tumor model, implying that the HF-LPLI-elicited immunological effects were dependent on the mitochondrial superoxide anion burst.
  
  
  METHODS
  In this study, for the first time, we show that HF-LPLI mediates tumor-killing effects via targeting photoinactivation of respiratory chain oxidase to trigger a superoxide anion burst, leading to a high level of oxidatively modified moieties, which contributes to the phenotypic changes in macrophages and mediates the antitumor immune response.
  
  
  CONCLUSIONS
  Our results suggest that HF-LPLI may be an effective cancer treatment modality that both eradicates the treated primary tumors and induces an antitumor immune response via photoinactivation of respiratory chain oxidase to trigger superoxide anion burst.
authors.affiliation: 1 MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , Guangzhou, China .
authors.forename: Cuixia
authors.initials: C
authors.lastname: Lu
authors.affiliation: 1 MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , Guangzhou, China .|2 Joint Laboratory of Laser Oncology with Cancer Center of Sun Yat-sen University, South China Normal University , Guangzhou, China .
authors.forename: Feifan
authors.initials: F
authors.lastname: Zhou
authors.affiliation: 1 MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , Guangzhou, China .|2 Joint Laboratory of Laser Oncology with Cancer Center of Sun Yat-sen University, South China Normal University , Guangzhou, China .
authors.forename: Shengnan
authors.initials: S
authors.lastname: Wu
authors.affiliation: 1 MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , Guangzhou, China .
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: 1 MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University , Guangzhou, China .|2 Joint Laboratory of Laser Oncology with Cancer Center of Sun Yat-sen University, South China Normal University , Guangzhou, China .
authors.forename: Da
authors.initials: D
authors.lastname: Xing
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004579:Electron Transport; D005260:Female; D006801:Humans; D028022:Low-Level Light Therapy / Q000379:methods; D008262:Macrophage Activation / Q000276:immunology / Q000528:radiation effects; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000528:radiation effects; D019255:NADPH Oxidases / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D010084:Oxidation-Reduction / Q000528:radiation effects; D010789:Phototherapy / Q000379:methods; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D047368:Tumor Burden / Q000528:radiation effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D013481:Superoxides; D019255:NADPH Oxidases; C022709:superoxide-forming enzyme