Prospects and feasibility of synergistic therapy with radiotherapy, immunotherapy, and DNA methyltransferase inhibitors in non-small cell lung cancer

Chen Jie; Rumeng Li; Yajie Cheng; Zhihao Wang; Qiuji Wu; Conghua Xie

doi:10.3389/fimmu.2023.1122352

Prospects and feasibility of synergistic therapy with radiotherapy, immunotherapy, and DNA methyltransferase inhibitors in non-small cell lung cancer

Front Immunol. 2023 Feb 17:14:1122352. doi: 10.3389/fimmu.2023.1122352. eCollection 2023.

Authors

Chen Jie^{1

2}, Rumeng Li^{1

2}, Yajie Cheng^{1

2}, Zhihao Wang^{1

2

3}, Qiuji Wu^{1

2

3}, Conghua Xie^{1

2

3}

Affiliations

¹ Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.
² Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan, China.
³ Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China.

Abstract

The morbidity and mortality of lung cancer are increasing, seriously threatening human health and life. Non-small cell lung cancer (NSCLC) has an insidious onset and is not easy to be diagnosed in its early stage. Distant metastasis often occurs and the prognosis is poor. Radiotherapy (RT) combined with immunotherapy, especially with immune checkpoint inhibitors (ICIs), has become the focus of research in NSCLC. The efficacy of immunoradiotherapy (iRT) is promising, but further optimization is necessary. DNA methylation has been involved in immune escape and radioresistance, and becomes a game changer in iRT. In this review, we focused on the regulation of DNA methylation on ICIs treatment resistance and radioresistance in NSCLC and elucidated the potential synergistic effects of DNA methyltransferases inhibitors (DNMTis) with iRT. Taken together, we outlined evidence suggesting that a combination of DNMTis, RT, and immunotherapy could be a promising treatment strategy to improve NSCLC outcomes.

Keywords: DMNTis; NSCLC; immunotherapy; radiotherapy; synergistic effect.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Non-Small-Cell Lung*
DNA
Feasibility Studies
Humans
Immunotherapy
Lung Neoplasms*
Methyltransferases

Substances

Methyltransferases
DNA

Grants and funding

This work was supported by National Natural Science Foundation of China (grant number 81972852), Key Research & Development Project of Hubei Province (grant number 2020BCA069), Health Commission of Hubei Province Medical Leading Talent Project, and Chinese Society of Clinical Oncology TopAlliance Tumor Immune Research Fund (grant number Y-JS2019-036).