Dipeptidyl peptidase 4 inhibition sensitizes radiotherapy by promoting T cell infiltration

Dipeptidyl peptidase 4 inhibition sensitizes radiotherapy by promoting T cell infiltration

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 re...

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Main Authors: Yu Tian, Lingyi Kong, Yan Li, Zhiyun Liao, Xing Cai, Suke Deng, Xiao Yang, Bin Zhang, Yijun Wang, Zhanjie Zhang, Bian Wu, Lu Wen, Fang Huang, Yan Hu, Chao Wan, Yifei Liao, Yajie Sun, Kunyu Yang
Format: Article
Language:English
Published: Taylor & Francis Group 2023-12-01
Series:OncoImmunology
Subjects:
Chemokines
DPP4
immunotherapy
radiotherapy
T cells
Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2023.2268257
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Summary: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.
ISSN:2162-402X

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