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Stereotactic ablative radiotherapy and FAPα-based cancer vaccine suppresses metastatic tumor growth in 4T1 mouse breast cancer

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收录情况： ◇ SCIE

作者：
Chen Meihua[1,*1] ; Xiao Ling[1] ; Jia Hongyuan[1] ; Wang Shubin[1] ; Jiang Xiao[1,2] ; Lei Xudan[1] ; Zhai Qiming[3] ; Lang Jinyi[1] ;
机构： [1]Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital &Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China [2]Institute of Isotope, China Institute of Atomic Energy, Beijing, China [3]Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory ofOral Biomedical Engineering of Higher Education, Chongqing, China
出处：
DOI： 10.1016/j.radonc.2023.109946
ISSN：

关键词： Stereotactic ablative radiotherapy Cancer vaccine Fibroblast activation protein-alpha Cancer-associated fibroblas tTumor microenvironment

摘要：
This study tested the hypothesis that a novel combination of stereotactic ablation radiotherapy (SABR) and a cancer vaccine against fibroblast activation protein-alpha (FAPα) can suppress established tumor growth and impede potential metastasis.The poorly immunogenic metastatic mouse mammary carcinoma 4T1 was used as a model. Mice were randomly assigned to five treatment groups: (1) untreated control, (2) FAPα-based cancer vaccine, (3) SABR, (4) SABR + pCDH (lentiviral control vector), (5) SABR + FAPα-based cancer vaccine (SABR/FAPα-Vax). FAPα-based cancer vaccine were administered subcutaneously every week for a total of three treatments. SABR was delivered to the primary tumor by 3 × 8 Gy after the first vaccination.Consistent with the poorly immunogenic nature of 4T1, tumor-bearing mice receiving FAPα-based cancer vaccine or SABR monotherapy showed a modest reduction in tumor volume and increased animal lifespan. In contrast, SABR/FAPα-Vax was well-tolerated, significantly reduced tumor burden, and increased survival compared to monotherapy. The increased survival correlated with inhibition of extracellular matrix (ECM) production, tumor vascularization and lymphangiogenesis. SABR/FAPα-Vax also resulted in an abscopal effect capable of eliminating lung metastases. SABR/FAPα-Vax recruited and activated CD8 + T cells to attack tumor cells and FAPα + stromal cells, and initiated suppressor cell reprogramming, including facilitating macrophage polarization toward an anti-tumor (M1) state, as well as depleting myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs).These findings provide a novel therapeutic combination of radiation and FAPα-based cancer vaccine with promising results against poorly immunogenic metastatic cancer. This study may pave the way to overcome the therapeutic resistance caused by FAPα + CAFs.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

基金：
This work was supported by the National Nature Science Foundationof China (81703070), Natural Science Foundation of Sichuan Province(2023NSFSC0708, 2020YJ0446), and Beijing Xisike Clinical OncologyResearch Foundation (Y-XD202001-0024)
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外文
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中科院(CAS)分区：
出版当年[2023]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学 2 区 核医学
最新[2023]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学 2 区 核医学
JCR分区：
出版当年[2023]版：
Q1 ONCOLOGY Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
最新[2023]版：
Q1 ONCOLOGY Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

影响因子： 最新[2023版] 最新五年平均 出版当年[2023版] 出版当年五年平均 出版前一年[2022版]

第一作者：
第一作者机构： [1]Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital &Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China [*1]No. 55 Renmin South Road, Chengdu 610041, Sichuan, China.
通讯作者：
通讯机构： [1]Department of Radiation Oncology, Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital &Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China [*1]No. 55 Renmin South Road, Chengdu 610041, Sichuan, China.
推荐引用方式(GB/T 7714)：
Chen Meihua,Xiao Ling,Jia Hongyuan,et al.Stereotactic ablative radiotherapy and FAPα-based cancer vaccine suppresses metastatic tumor growth in 4T1 mouse breast cancer[J].RADIOTHERAPY AND ONCOLOGY.2023,189:doi:10.1016/j.radonc.2023.109946.
APA：
Chen Meihua,Xiao Ling,Jia Hongyuan,Wang Shubin,Jiang Xiao...&Lang Jinyi.(2023).Stereotactic ablative radiotherapy and FAPα-based cancer vaccine suppresses metastatic tumor growth in 4T1 mouse breast cancer.RADIOTHERAPY AND ONCOLOGY,189,
MLA：
Chen Meihua,et al."Stereotactic ablative radiotherapy and FAPα-based cancer vaccine suppresses metastatic tumor growth in 4T1 mouse breast cancer".RADIOTHERAPY AND ONCOLOGY 189.(2023)

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