Chen Lichao, Imamichi Shoji, Tong Ying, Sasaki Yuka, Onodera Takae, Nakamura Satoshi, Igaki Hiroshi, Itami Jun, Masutani Mitsuko
Department of Molecular and Genomic Biomedicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523, Japan.
Radioisotope Division, Lab of Collaborative Research, Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
Medicines (Basel). 2021 Jul 4;8(7):35. doi: 10.3390/medicines8070035.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes dendritic cell differentiation from precursors, and consequently, enhances the antigen presentation process and adaptive immune responses. With such functions, GM-CSF has been used as immunotherapy in combination with radiotherapy for cancer treatment to augment the survival and activity of immune cells. However, an immune-suppressive tumor microenvironment may cause anergy of T cells. It has also been reported that GM-CSF contributes to the development of myeloid-derived suppressor cells from the precursors. In this study, to analyze the combined effect of GM-CSF and released factors from cancer cells after gamma-ray irradiation on bone marrow cell differentiation and dynamics, we established an in vitro culture system using mouse bone marrow cells, GM-CSF, and conditioned medium from gamma ray irradiated mouse melanoma B16 cells at 24 Gy. We analyzed the gene expression changes of the bone marrow-derived cells on day 6. The results showed that GM-CSF dose-dependently enhanced the differentiation of macrophages from bone marrow cells, their antigen-presenting function and polarization to type I. The results implied the induced macrophages from the bone marrow may potentially contribute to tumor immune responses in a systemic manner when GM-CSF is boosted during photon-beam radiation therapy.
粒细胞-巨噬细胞集落刺激因子（GM-CSF）可促进前体细胞向树突状细胞分化，进而增强抗原呈递过程和适应性免疫反应。基于这些功能，GM-CSF已被用作免疫疗法，与放射疗法联合用于癌症治疗，以提高免疫细胞的存活率和活性。然而，免疫抑制性肿瘤微环境可能导致T细胞无反应性。也有报道称，GM-CSF有助于前体细胞发育为髓源性抑制细胞。在本研究中，为了分析GM-CSF与γ射线照射后癌细胞释放因子对骨髓细胞分化和动态变化的联合作用，我们利用小鼠骨髓细胞、GM-CSF和来自经24 Gyγ射线照射的小鼠黑色素瘤B16细胞的条件培养基建立了体外培养系统。我们分析了第6天骨髓来源细胞的基因表达变化。结果表明，GM-CSF剂量依赖性地增强了骨髓细胞向巨噬细胞的分化、其抗原呈递功能以及向I型的极化。结果表明，当在光子束放射治疗期间GM-CSF增加时，骨髓诱导的巨噬细胞可能以全身方式潜在地促进肿瘤免疫反应。
