Sub-acute Toxicity in Non-cancerous Tissue and Immune-Related Adverse Events of a Novel Combination Therapy for Cancer
Sub-acute Toxicity in Non-cancerous Tissue and Immune-Related Adverse Events of a Novel Combination Therapy for Cancer
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DOI：
10.3389/fonc.2019.01504
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发表时间：
2020-01-14
影响因子：
4.7
通讯作者：
Howell, Viive M.
中科院分区：
文献类型：
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作者：
McKelvey, Kelly J.;Hudson, Amanda L.;Howell, Viive M.
当使用免疫肿瘤药物或放射治疗时，脑、肺和结肠组织会经历有害的免疫相关不良事件。然而，关于在免疫肿瘤治疗方案中加入辐射是否会加剧组织炎症反应的信息缺乏。我们使用小鼠模型来评估C57Bl/6小鼠在对正常脑、肺或结肠组织进行全身抗程序性细胞死亡蛋白1 （α PD-1）免疫治疗或联合立体定向分形10灰/5 x射线照射时的亚急性组织损伤和全身免疫反应。该模型表明，联合α - PD-1免疫治疗和放射治疗可改变正常的结肠细胞增殖和脑血管系统，并诱导全身血小板减少、淋巴细胞减少、免疫抑制和免疫库（包括白细胞介素-1 β）改变。因此，我们的数据支持在接受联合治疗的患者中密切监测血液学和免疫相关不良事件。
Brain, lung, and colon tissue experience deleterious immune-related adverse events when immune-oncological agents or radiation are administered. However, there is a paucity of information regarding whether the addition of radiation to immuno-oncological regimens exacerbates the tissue inflammatory response. We used a murine model to evaluate sub-acute tissue damage and the systemic immune response in C57Bl/6 mice when administered systemic anti-programmed cell death protein 1 (alpha PD-1) immunotherapy alone or in combination with stereotactic fractionated 10 gray/5 X-ray radiation to normal brain, lung or colon tissue. The model indicated that combinatorial alpha PD-1 immunotherapy and radiation may alter normal colon cell proliferation and cerebral blood vasculature, and induce systemic thrombocytopenia, lymphopenia, immune suppression, and altered immune repertoire (including interleukin-1 beta). Therein our data supports close monitoring of hematological and immune-related adverse events in patients receiving combination therapy.