LILRB2 inhibition enhances radiation sensitivity in non-small cell lung cancer by attenuating radiation-induced senescence

被引：8

作者：

Chen, Xiaozheng ^{[1
,2
]}

Yuan, Meng ^{[1
,2
,3
]}

Zhong, Tao

Wang, Minglei ^{[4
]}

Wu, Fei ^{[1
,2
]}

Lu, Jie ^{[1
,2
]}

Sun, Dongfeng ^{[1
,2
]}

Xiao, Changyan ^{[1
,2
]}

Sun, Yuping ^{[1
]}

Hu, Yun ^{[5
]}

Wu, Meng ^{[1
,2
]}

Wang, Linlin ^{[6
,9
]}

Yu, Jinming ^{[1
,2
,7
]}

Chen, Dawei ^{[1
,2
,8
]}

机构：

[1] Shandong First Med Univ & Shandong Acad Med Sci, Dept Radiat Oncol, 440 Jiyan Rd, Jinan 250117, Shandong, Peoples R China

[2] Shandong First Med Univ & Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Shandong Prov Key Lab Radiat Oncol, 440 Jiyan Rd, Jinan 250117, Shandong, Peoples R China

[3] Jining Med Univ, Clin Med Coll, Jining, Shandong, Peoples R China

[4] Shandong First Med Univ & Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Dept Oncol, Jinan, Peoples R China

[5] Univ Texas M D Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX USA

[6] Shandong First Med Univ & Shandong Acad Med Sci, Shandong Canc Hosp & Inst, Dept Radiat Oncol, Jinan, Shandong, Peoples R China

[7] Chinese Acad Med Sci, Res Unit Radiat Oncol, 440 Jiyan Rd, Jinan 250117, Shandong, Peoples R China

[8] Shandong Univ, Canc Ctr, Dept Radiat Oncol, Jinan, Shandong, Peoples R China

[9] 440 Jiyan Rd, Jinan 250117, Shandong, Peoples R China

来源：

CANCER LETTERS | 2024年 / 593卷

关键词：

LILRB2; Non -small cell lung cancer; Cell senescence; Radiotherapy; RECEPTOR B2; ILT4; EXPRESSION; BIOMARKER; PROMOTES; THERAPY;

D O I：

10.1016/j.canlet.2024.216930

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Radiotherapy (RT) in non -small cell lung cancer (NSCLC) triggers cellular senescence, complicating tumor microenvironments and affecting treatment outcomes. This study examines the role of lymphocyte immunoglobulin-like receptor B2 (LILRB2) in modulating RT-induced senescence and radiosensitivity in NSCLC. Through methodologies including irradiation, lentivirus transfection, and various molecular assays, we assessed LILRB2 's expression and its impact on cellular senescence levels and tumor cell behaviors. Our findings reveal that RT upregulates LILRB2, facilitating senescence and a senescence-associated secretory phenotype (SASP), which in turn enhances tumor proliferation and resistance to radiation. Importantly, LILRB2 silencing attenuates these effects by inhibiting the JAK2/STAT3 pathway, significantly increasing radiosensitivity in NSCLC models. Clinical data correlate high LILRB2 expression with reduced RT response and poorer prognosis, suggesting LILRB2 's pivotal role in RT-induced senescence and its potential as a therapeutic target to improve NSCLC radiosensitivity.

引用

页数：14

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