Metastatic lymph nodes (MLNs) are one of the most common causes of distant metastasis, and their presence signals a serious deterioration in the life prognosis of an affected patient. The treatment of MLNs at an early stage is necessary to inhibit metastases to distant LNs and organs. Radiation therapy is an effective therapeutic modality for local tumor control in many cancers, and its effect is enhanced by fractionated radiation therapy or in combination with other therapeutic regimens. In addition, recent studies have reported that total body irradiation (TBI) increases the activation of immune cells such as NK cells and infiltration of CD4+ T cells to tumor tissue. However, the effects of TBI on LN metastasis remains unclear. This study assessed the effect of TBI by changing the radiation dose and number of irradiations in an MLN mouse model. To induce metastasis into the proper axillary lymph node (PALN) and lung, mouse breast cancer FM3A-Luc cells were inoculated into the subiliac lymph node (SiLN) of MXH10/Mo/lpr mice. Mice were assigned to 4 groups thus: received no TBI; received a single dose of 0.2 Gy as low-dose TBI (single L-TBI); received a single dose of 1.0 Gy as middle-dose TBI (single M-TBI); or received two fractions of 2.0 Gy (fractionated M-TBI). The irradiation was carried out on day 4 post-inoculation in the single L-TBI and M-TBI groups. In the fractionated M-TBI group the irradiation was carried out on days 4 and 7 post-inoculation. Tumor growth was evaluated using an in vivo bioluminescence imaging system. In the non-irradiated group, tumor activity in the SiLN and PALN increased over time and lung metastasis was confirmed on day 28 post-inoculation. In addition, the single L-TBI dose did not delay tumor growth in the SiLN and PALN or inhibit lung metastasis. In other words, the tumor activity was not significantly changed compared to the non-irradiated group. Single and fractionated M-TBI doses significantly delayed tumor growth in the SiLN and PALN and inhibited lung metastasis. Furthermore, the fractionated M-TBI group exhibited the greatest delay in tumor growth in the PALN compared to the other three groups. These results suggest that the TBI at a dose > 1.0 Gy can delay tumor growth of MLNs in the early stage and distant metastasis. Moreover, the radiation dose and number of irradiations may be essential factors for enhancing the anti-tumor effects of TBI. We anticipate that TBI will contribute to the prevention and treatment of cancer metastasis via LNs.

Citation Format: Shouta Sora, Radhika Mishra, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama. Possibility of total body irradiations for lymph node metastasis and lung metastasis [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr LBA049.