title: Modulated electro-hyperthermia enhances dendritic cell therapy through an abscopal effect in mice.
abstract: The aim of this study was to assess whether modulated electro-hyperthermia (mEHT) can induce an abscopal effect and thereby enhance the antitumor effects of immunotherapy. We used an intratumoral dendritic cell (DC) injection and mEHT to treat C3H/He mice inoculated with squamous cell carcinoma SCCVII cells in the left leg, and we assessed the whole body antitumor effects. Tumors were examined every two or three days in order to assess growth inhibition. The tumor-draining lymph nodes were removed to enable flow cytometric analysis of CD3+ and CD8+ cells, whereas immunohistochemistry was used to assess CD8, S100 and Foxp3 expression in the tumors. Additionally, GP96 expression in the tumors from the different treatment groups was measured. In the control group, the mean tumor volume was larger than that in other groups. These results indicated that the combination therapy of an intratumoral DC injection and mEHT evoked systemic antitumor activity. A larger number of CD3+ and CD8+ cells were detected by flow cytometric analysis in the DC plus mEHT treatment group. Tumor tissue immunostaining showed that CD8 and S100 were more strongly expressed in the DC plus mEHT treatment group, although Foxp3 expression was much higher in the control group. The GP96 gene expression level in the mEHT group was significantly different from the expression level in the control group. An abscopal effect may be induced by mEHT, and the effect of immunotherapy with DCs was strongly enhanced by the overexpression of GP96. GP96 is thought to be one of the molecules explaining the abscopal effect. Direct intratumoral administration of DCs and mEHT may be a feasible future treatment strategy.
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Wei
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Akutsu
authors.affiliation: Department of Veterinary Clinical Medicine, Faculty of Veterinary Science, Tottori University, Tottoti 680-8553, Japan.
authors.forename: Gabor
authors.initials: G
authors.lastname: Andocs
authors.affiliation: Department of Bioinformatics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Suganami
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Gulbostan
authors.initials: G
authors.lastname: Yusup
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Komatsu-Akimoto
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Isamu
authors.initials: I
authors.lastname: Hoshino
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Hanari
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Mikito
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Isozaki
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Akanuma
authors.affiliation: Department of Bioinformatics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: Hisahiro
authors.initials: H
authors.lastname: Matsubara
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D007167:Immunotherapy; D008562:Membrane Glycoproteins / Q000378:metabolism; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000276:immunology; D013899:Thoracic Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*
chemical_list: D008562:Membrane Glycoproteins; C053387:endoplasmin