Comparative analysis of the immune responses in cancer cells irradiated with X-ray, proton and carbon-ion beams
Comparative analysis of the immune responses in cancer cells irradiated with X-ray, proton and carbon-ion beams
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DOI：
10.1016/j.bbrc.2021.11.004
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发表时间：
2021-11-14
影响因子：
3.1
通讯作者：
Akimoto, Tetsuo
中科院分区：
文献类型：
--
作者：
Du, Junyan;Kageyama, Shun-Ichiro;Akimoto, Tetsuo
放射治疗（RT）是癌症的有效治疗选择;然而，其疗效在局部晚期癌症中仍低于最佳。基于免疫检查点的治疗，包括抗PD-L1抗体的施用，是一种与RT协同作用的有前途的方法。质子束治疗和碳离子治疗是癌症患者的常见选择。据报道，质子和碳离子可诱导癌细胞的免疫反应;然而，其潜在机制仍不清楚。在这里，我们的目的是比较辐射（IR）与X射线，质子和碳离子在食管癌细胞系和潜在的机制。食管癌细胞系KYSE 450用1分/15 GyE（戈伊当量）的X射线、质子或碳离子束照射，然后收获细胞用于RNA测序和基因富集分析。我们还淘汰了STING和STAT 1，以寻求机械的见解。RNA测序数据显示，KYSE 450在IR后6-24 h用X射线、质子和碳离子束照射后，基因表达特征和生物学过程是不同的。然而，3天后，检测到一个共同的基因表达特征，与参与先天免疫反应的生物学途径相关。基因敲除实验表明，STING-STAT 1轴是IR后免疫反应的基础。X射线、质子和碳离子IR诱导类似的免疫反应，由STING-STAT 1轴调节。(c)2021年，任作家。爱思唯尔公司出版这是一篇在CC BY许可证下的开放获取文章（http：//creativecommons.org/licenses/by/4.0/）。
Radiotherapy (RT) is an effective treatment option for cancer; however, its efficacy remains less than optimal in locally advanced cancer. Immune checkpoint inhibitor-based therapy, including the administration of anti-PD-L1 antibodies, is a promising approach that works synergistically with RT. Proton beam therapy and carbon-ion therapy are common options for patients with cancer. Proton and carbon ions are reported to induce an immune reaction in cancer cells; however, the underlying mechanisms remain unclear. Here, we aimed to compare the immune responses after irradiation (IR) with X-ray, protons, and carbon ions in an oesophageal cancer cell line and the underlying mechanisms. An oesophageal cancer cell line, KYSE450, was irradiated with 1 fraction/15 GyE (Gy equivalent) of X-ray, proton, or carbon-ion beams, and then, the cells were harvested for RNA sequencing and gene enrichment analysis. We also knocked out STING and STAT1 in the quest for mechanistic insights. RNA sequencing data revealed that gene expression signatures and biological processes were different in KYSE450 irradiated with X-ray, proton, and carbon-ion beams 6-24 h after IR. However, after 3 days, a common gene expression signature was detected, associated with biological pathways involved in innate immune responses. Gene knock-out experiments revealed that the STING-STAT1 axis underlies the immune reactions after IR. X-Ray, proton, and carbon-ion IRs induced similar immune responses, regulated by the STING-STAT1 axis. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).