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KMID : 1038620220400010053
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Radiation Oncology Journal
2022 Volume.40 No. 1 p.53 ~ p.65
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Immunomodulatory effect of splenectomy in lung cancer mouse xenograft models receiving radiation therapy
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Kim Ye-Eun
Choi Chang-Hoon
Park Jee-Hyun
Ahn Won-Gyun
Shin Sung-Won
Kim Shin-Yeong
Noh Jae-Myoung
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Abstract
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Purpose: This study aims to investigate the effect of splenectomy on radiation-mediated growth inhibition and immune modulation in lung cancer xenograft models.
Materials and Methods: Human non-small cell lung cancer H1299 cells and murine Lewis lung carcinoma LL/2-luc cells were injected into the right hind leg of BALB/c-nude mice and C57BL/6 mice, respectively. Splenectomy or sham operation was performed prior to tumor cell injection or before and after irradiation during tumor growth. Irradiation was delivered with 2?3 fractions of 6 Gy X-ray using a linear accelerator. Flow cytometry analysis was performed for immune cell profiling.
Results: Splenectomy prior to tumor injection or at early stage inhibited growth of LL/2-luc tumors but not that of H1299 tumors; however, it did not enhance the antitumor effect of radiation regardless of intervention timing. Flow cytometry analysis showed monocytic myeloid-derived suppressor cells (MDSCs) and activated CD8+ T cells increased after irradiation in the tumors of splenectomized mice, compared to those of sham-operated mice. Administration of anti-PD-1 (programmed death-1) antibodies improved the ability of splenectomy to attenuate the growth of irradiated tumors.
Conclusion: Splenectomy has paradoxical effects on radiation-induced tumor growth inhibition, depending on tumor types and intervention timing, but it has an immune-modulating effect when combined with radiation.
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KEYWORD
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Radiotherapy, Myeloid-derived suppressor cells, Splenectomy, Lung neoplasms
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