title: In vivo immunological antitumor effect of OK-432-stimulated dendritic cell transfer after radiofrequency ablation.
abstract: Radiofrequency ablation therapy (RFA) is a radical treatment for liver cancers and induces tumor antigen-specific immune responses. In the present study, we examined the antitumor effects of focal OK-432-stimulated dendritic cell (DC) transfer combined with RFA and analyzed the functional mechanisms involved using a murine model. C57BL/6 mice were injected subcutaneously with colon cancer cells (MC38) in their bilateral flanks. After the establishment of tumors, the subcutaneous tumor on one flank was treated using RFA, and then OK-432-stimulated DCs were injected locally. The antitumor effect of the treatment was evaluated by measuring the size of the tumor on the opposite flank, and the immunological responses were assessed using tumor-infiltrating lymphocytes, splenocytes and draining lymph nodes. Tumor growth was strongly inhibited in mice that exhibited efficient DC migration after RFA and OK-432-stimulated DC transfer, as compared to mice treated with RFA alone or treatment involving immature DC transfer. We also demonstrated that the antitumor effect of this treatment depended on both CD8-positive and CD4-positive cells. On the basis of our findings, we believe that combination therapy for metastatic liver cancer consisting of OK-432-stimulated DCs in combination with RFA can proceed to clinical trials, and it is anticipated to be markedly superior to RFA single therapy.
authors.affiliation: Disease Control and Homeostasis, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan, hidetoshi.naka@gmail.com.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Eishiro
authors.initials: E
authors.lastname: Mizukoshi
authors.forename: Noriho
authors.initials: N
authors.lastname: Iida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Terashima
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kitahara
authors.forename: Yohei
authors.initials: Y
authors.lastname: Marukawa
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kitamura
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Nakamoto
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Hiroishi
authors.forename: Michio
authors.initials: M
authors.lastname: Imawari
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017115:Catheter Ablation; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D008207:Lymphatic Metastasis; D008212:Lymphocyte Depletion; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D010844:Picibanil / Q000494:pharmacology*; D040521:Subcutaneous Tissue; D016176:T-Lymphocyte Subsets / Q000276:immunology; D047368:Tumor Burden
chemical_list: D000276:Adjuvants, Immunologic; D010844:Picibanil; D007371:Interferon-gamma