放射治疗
癌症研究
趋化因子
肿瘤微环境
免疫疗法
医学
免疫系统
渗透(HVAC)
CD8型
T细胞
免疫学
内科学
物理
热力学
作者
Yu Tian,Ling‐Yi Kong,Yan Li,Zhiyun Liao,Xiujun Cai,Suke Deng,Yang Xiao,Bin Zhang,Yijun Wang,Zhanjie Zhang,Bian Wu,Lu Wen,Fen Huang,Yan Hu,Chao Wan,Yijie Liao,Yajie Sun,Kunyu Yang
出处
期刊:OncoImmunology
[Informa]
日期:2023-10-12
卷期号:12 (1)
标识
DOI:10.1080/2162402x.2023.2268257
摘要
Radiotherapy could regulate systemic antitumor immunity, while the immune state in the tumor microenvironment (TME) also affects the efficacy of radiotherapy. We have found that higher CD8+ T cell infiltration is associated with longer overall survival of lung adenocarcinoma and melanoma patients receiving radiotherapy. 8-Gray radiation increased the transcriptional levels of chemokines in tumor cells in vitro. However, it was not sufficient to induce significant lymphocyte infiltration in vivo. Dipeptidyl peptidase 4 (DPP4) has been reported to inactivate chemokines via post-translational truncation. Single-cell sequencing revealed that dendritic cells (DCs) had a higher DPP4 expression among other cells in the TME and upregulated DPP4 expression after radiation. Combining a DPP4 inhibitor with radiotherapy could promote chemokines expression and T cell infiltration in the TME, enhancing the antitumor effect of radiotherapy. Moreover, this therapy further enhanced the therapeutic efficacy of anti-PD-1. In this study, we demonstrated the underlying mechanism of why radiotherapy failed to induce sufficient T cell infiltration and proposed an effective strategy to promote T cell infiltration and sensitize radiotherapy. These findings demonstrate the translational value of DPP4 inhibition as a complementary approach to enhance the efficacy of radiotherapy and the combination of radiotherapy with immunotherapy.
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