Th Balance-Related Host Genetic Background Affects the Therapeutic Effects of Combining Carbon-Ion Radiation Therapy With Dendritic Cell Immunotherapy

Liqiu Ma; Yoshimitsu Sakamoto; Ken Ando; Hidetoshi Fujita; Akihisa Takahashi; Tsuguhide Takeshima; Hiromi Otsuka; Daniel K Ebner; Kazuhiro Kakimi; Takashi Imai; Takashi Shimokawa

doi:10.1016/j.ijrobp.2021.10.141

Th Balance-Related Host Genetic Background Affects the Therapeutic Effects of Combining Carbon-Ion Radiation Therapy With Dendritic Cell Immunotherapy

Int J Radiat Oncol Biol Phys. 2022 Mar 1;112(3):780-789. doi: 10.1016/j.ijrobp.2021.10.141. Epub 2021 Nov 3.

Authors

Affiliations

¹ National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan; Gunma University Heavy Ion Medical Center, Gunma, Japan; China Institute of Atomic Energy, Beijing, China.
² National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.
³ National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan; Department of Radiation Oncology, Gunma University Graduate School of Medicine, Gunma, Japan.
⁴ Gunma University Heavy Ion Medical Center, Gunma, Japan.
⁵ Department of Immunotherapeutics, The University of Tokyo, Tokyo, Japan.
⁶ National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan. Electronic address: shimokawa.takashi@qst.go.jp.

PMID: 34740767
DOI: 10.1016/j.ijrobp.2021.10.141

Abstract

Purpose: The goal of this study is to clarify the underlying mechanisms of metastasis suppression by carbon-ion radiotherapy combined with immature dendritic cell immunotherapy (CiDC), which was shown previously to suppress pulmonary metastasis in an NR-S1-bearing C3H/He mouse model.

Methods and materials: Mouse carcinoma cell lines (LLC, LM8, Colon-26, and Colon-26MGS) were grafted into the right hind paw of syngeneic mice (C57BL/6J, C3H/He, and BALB/c). Seven days later, the tumors on the mice were locally irradiated with carbon ions (290 MeV/n, 6 cm spread-out Bragg peak, 1 or 2 Gy). At 1.5 days after irradiation, bone marrow-derived immature dendritic cells (iDCs) were administrated intravenously into a subset of the mice. The number of lung metastases was evaluated within 3 weeks after irradiation. In vitro-cultured cancer cells were irradiated with carbon ions (290 MeV/n, mono-energy, LET approximately 70-80 keV/µm), and then cocultured with iDCs for 3 days to determine the DC maturation.

Results: CiDC effectively repressed distant lung metastases in cancer cell (LLC and LM8)-bearing C57BL/6J and C3H/He mouse models. However, Colon-26- and Colon-26MGS-bearing BALB/c models did not show enhancement of metastasis suppression by combination treatment. This result was evaluated further by comparing LM8-bearing C3H/He and LLC-bearing C57BL/6J models with a Colon-26-bearing BALB/c model. In vitro coculture assays demonstrated that all irradiated cell lines were able to activate C3H/He- or C57BL/6J-derived iDCs into mature DCs, but not BALB/c-derived iDCs.

Conclusions: The genetic background of the host could have a strong effect on the potency of combination therapy. Future animal and clinical testing should evaluate host genetic factors when evaluating treatment efficacy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Carbon
Dendritic Cells
Genetic Background
Immunotherapy*
Lung Neoplasms* / genetics
Lung Neoplasms* / radiotherapy
Mice
Mice, Inbred C3H
Mice, Inbred C57BL

Substances

Carbon