文献类型：期刊文献

英文题名：Carbon ion irradiation combined with PD-1 inhibitor trigger abscopal effect in Lewis lung cancer via a threshold dose

作者：Liu, Ruifeng[1,4];Geng, Yichao[1,2,3];Luo, Hongtao[1];Zhang, Qiuning[1];Yang, Zhen[5];Li, Shan[3];Sun, Shilong[1];Liu, Zhiqiang[1];Dong, Meng[3];Du, Tianqi[3];Che, Tuanjie[6];Wang, Xiaohu[1,2,6]

第一作者：Liu, Ruifeng

通信作者：Zhang, QN[1];Wang, XH[1];Zhang, QN[2];Wang, XH[2]

机构：[1]Chinese Acad Sci, Inst Modern Phys, Lanzhou, Peoples R China;[2]Lanzhou Univ, Sch Clin Med 1, Lanzhou, Peoples R China;[3]Guizhou Med Univ, Affiliated Canc Hosp, Guiyang, Peoples R China;[4]Wuhan Renmin Hosp Univ, Hosp Econ & Technol Dev Zone, Heavy Ion Med Ctr, Wuhan, Peoples R China;[5]Gansu Univ Tradit Chinese Med, Lanzhou, Peoples R China;[6]Key Lab Funct Genom & Mol Diagnost Gansu Prov, Lanzhou, Peoples R China

第一机构：Chinese Acad Sci, Inst Modern Phys, Lanzhou, Peoples R China

通信机构：[1]corresponding author), Chinese Acad Sci, Inst Modern Phys, Lanzhou, Peoples R China;[2]corresponding author), 1 Yanxia Rd, Lanzhou, Gansu, Peoples R China.

年份：2024

卷号：15

期号：8

起止页码：2245

外文期刊名：JOURNAL OF CANCER

收录：;Scopus(收录号：2-s2.0-85187666425);WOS:【SCI-EXPANDED(收录号:WOS:001255874700012)】；

基金：Funding This work was supported by Talent innovation and venture project of Lanzhou city (No. 2021-RC-125) , and China Foundation for International Medical Exchange (No. Z-2017-24-2108) , the National Key R&D Project (No. 2022YFC2401505) , the authorized project of Lanzhou KejinTaiji Corporation, Ltd (No.1100090018) , Gansu Provincial Association for Science and Technology Innovation Drive Assistance Project (No. GXH20220617-3) , and Science and Technology Project of Gansu Province (No. 22CX8JA149) .

语种：英文

外文关键词：Carbon ion; Irradiation; PD-1 inhibitor; In vitro experiment; Abscopal effect

摘要：Background and goal: Carbon ion beam is radio -biologically more efficient than photons and is beneficial for treating radio -resistant tumors. Several animal experiments with tumor -bearing suggest that carbon ion beam irradiation in combination with immunotherapy yields better results, especially in controlling distant metastases. This implies that carbon ion induces a different anti -tumor immune response than photon beam. More complex molecular mechanisms need to be uncovered. This in vivo and in vitro experiment was carried out in order to examine the radio -immune effects and the mechanism of action of carbon ion beam versus X-ray in combination with PD -1 inhibitors. Methods and Materials: Lewis lung adenocarcinoma cells and C57BL/6 mice were used to create a tumor -bearing mouse model, with the non -irradiated tumor growing on the right hind leg and the irradiated tumor on the left rear. 10Gy carbon ion beam or X-ray radiation, either alone or in combination with PD -1 inhibitor, were used to treat the left back tumor. The expression of molecules linked to immunogenicity and the infiltration of CD8+ T lymphocytes into tumor tissues were both identified using immunohistochemistry. IFN- beta in mouse serum was measured using an ELISA, while CD8+ T cells in mouse peripheral blood were measured using flow cytometry. Lewis cells were exposed to different dose of X-ray and carbon ion. TREX1, PD -L1, and IFN- beta alterations in mRNA and protein levels were identified using Western blot or RT-PCR, respectively. TREX1 knockdown was created by siRNA transfection and exposed to various radiations. Using the CCK8 test, EdU assay, and flow cytometry, changes in cell viability, proliferation, and apoptosis rate were discovered. Results: Bilateral tumors were significantly inhibited by the use of carbon ion or X-ray in combination with PD -1, particularly to non -irradiated tumor(p<0.05). The percentage of infiltrating CD8+ T cells and the level of IFN- beta expression were both raised by 10Gy carbon ion irradiation in the irradiated side tumor, although PD -L1 and TREX1 expression levels were also elevated. Lewis cell in vitro experiment further demonstrated that both X-ray and carbon ion irradiation can up -regulate the expression levels of PD -L1 and TREX1 with dose -dependent in tumors, particularly the trend of up -regulation TREX1 is more apparent at a higher dose in carbon ion, i.e. 8 or 10Gy, while the level of IFN- beta is decreased. IFN- beta levels were considerably raised under hypofractionated doses of carbon ion radiation by gene silencing TREX1. Conclusions: By enhancing tumor immunogenicity and increasing CD8+T infiltration in TME through a threshold dosage, X-ray or carbon ion radiation and PD -1 inhibitors improve anti -tumor activity and cause abscopal effect in Lewis lung adenocarcinoma-bearing mice. TREX1 is a possible therapeutic target and prognostic marker.