Combination tumor immunotherapy with radiotherapy and Th1 cell therapy against murine lung carcinoma |
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Authors: | Hiroshi Yokouchi Kenji Chamoto Daiko Wakita Koichi Yamazaki Hiroki Shirato Tsuguhide Takeshima Hirotoshi Dosaka-Akita Masaharu Nishimura Zhang Yue Hidemitsu Kitamura Takashi Nishimura |
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Institution: | (1) Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo 060-0815, Japan;(2) First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan;(3) Division of Radiation Oncology, Department of Radiology, Hokkaido University School of Medicine, Sapporo, Japan;(4) Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan;(5) Division of ROYCE’ Health Bioscience, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan |
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Abstract: | Mice bearing established Lewis lung carcinoma (LLC) expressing model tumor antigen, ovalbumin (OVA) (LLC-OVA) marginally responded
to local radiotherapy, but none of the mice was cured. In contrast, treatment of the tumor-bearing mice with intratumoral
injection of tumor-specific T helper type 1 (Th1) cells and tumor antigen (OVA) after radiotherapy dramatically prolonged
the survival days and induced complete cure of the mice at high frequency (80%). Radiation therapy combined with Th1 cells
or OVA alone showed no significant therapeutic activity against LLC-OVA. Such a strong therapeutic activity was not induced
by intratumoral injection of Th1 cells plus OVA. Compared with other treatment, radiation therapy combined with Th1 cells
and OVA was superior to induce the generation of OVA/H-2b tetramer+ tumor-specific cytotoxic T lymphocyte (CTL) with a strong cytotoxicity against LLC-OVA in draining lymph node (DLN). Moreover,
the combined therapy is demonstrated to inhibit the growth of tumor mass, which grew at contralateral side. These results
indicated that radiotherapy combined with Th1 cell/vaccine therapy induced a systemic antitumor immunity. These findings suggested
that combination therapy with radiotherapy and Th1 cell/vaccine therapy may become a practical strategy for cancer treatment.
Hiroshi Yokouchi and Kenji Chamoto are equally contributed. |
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Keywords: | Draining lymph node Immunotherapy Irradiation Lung cancer Th1 cells |
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