In vivo immunological antitumor effect of OK-432-stimulated dendritic cell transfer after radiofrequency ablation

• DOI: 10.1007/s00262-013-1514-7
• Publication Date: 2014-01-02T14:09:01Z
• Authors: Hidetoshi Nakagawa; Eishiro Mizukoshi; Noriho Iida; Takeshi Terashima; Masaaki Kitahara; Yohei Marukawa; Kazuya Kitamura; Yasunari Nakamoto; Kazumasa Hiroishi; Michio Imawari; Shuichi Kaneko
• Keywords: CD4-Positive T-Lymphocytes; Dendritic Cells; Adenocarcinoma; CD8-Positive T-Lymphocytes; Combined Modality Therapy; Lymphocyte Depletion; 3. Good health; Mice, Inbred C57BL; Picibanil; Interferon-gamma; Mice; 03 medical and health sciences; Lymphocytes, Tumor-Infiltrating; Subcutaneous Tissue; 0302 clinical medicine; Adjuvants, Immunologic; Phagocytosis; Cell Movement; Lymphatic Metastasis; Catheter Ablation; Animals; Female; Colorectal Neoplasms

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.