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

作者全名："Chen, Meihua; Xiao, Ling; Jia, Hongyuan; Wang, Shubin; Jiang, Xiao; Lei, Xudan; Zhai, Qiming; Lang, Jinyi"

作者地址："[Chen, Meihua; Xiao, Ling; Jia, Hongyuan; Wang, Shubin; Jiang, Xiao; Lei, Xudan; Lang, Jinyi] Univ Elect Sci & Technol China, Dept Radiat Oncol, Radiat Oncol Key Lab Sichuan Prov, Sichuan Clin Res Ctr Canc,Sichuan Canc Hosp & Inst, Chengdu, Peoples R China; [Jiang, Xiao] China Inst Atom Energy, Inst Isotope, Beijing, Peoples R China; [Zhai, Qiming] Chongqing Med Univ, Stomatol Hosp, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China; [Chen, Meihua] 55 Renmin South Rd, Chengdu 610041, Sichuan, Peoples R China"

通信作者："Chen, MH (通讯作者)，55 Renmin South Rd, Chengdu 610041, Sichuan, Peoples R China."

来源：RADIOTHERAPY AND ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001099156100001

JCR分区：Q1

影响因子：4.9

年份：2023

卷号：189

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Stereotactic ablative radiotherapy; Cancer vaccine; Fibroblast activation protein -alpha; Cancer -associated fibroblast; Tumor microenvironment

摘要："Background and purpose: This study tested the hypothesis that a novel combination of stereotactic ablation radiotherapy (SABR) and a cancer vaccine against fibroblast activation protein-alpha (FAP alpha) can suppress established tumor growth and impede potential metastasis. Methods: 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) FAP alpha-based cancer vaccine, (3) SABR, (4) SABR + pCDH (lentiviral control vector), (5) SABR + FAP alpha-based cancer vaccine (SABR/FAP alpha-Vax). FAP alpha-based cancer vaccine were administered subcutaneously every week for a total of three treatments. SABR was delivered to the primary tumor by 3 x 8 Gy after the first vaccination.Results: Consistent with the poorly immunogenic nature of 4T1, tumor-bearing mice receiving FAP alpha-based cancer vaccine or SABR monotherapy showed a modest reduction in tumor volume and increased animal lifespan. In contrast, SABR/FAP alpha-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/FAP alpha-Vax also resulted in an abscopal effect capable of eliminating lung metastases. SABR/FAP alpha-Vax recruited and activated CD8 + T cells to attack tumor cells and FAP alpha + 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). Conclusion: These findings provide a novel therapeutic combination of radiation and FAP alpha-based cancer vaccine with promising results against poorly immunogenic metastatic cancer. This study may pave the way to overcome the therapeutic resistance caused by FAP alpha + CAFs."

基金机构："National Nature Science Foundation of China [81703070]; Natural Science Foundation of Sichuan Province [2023NSFSC0708, 2020YJ0446]; Beijing Xisike Clinical Oncology Research Foundation [Y-XD202001-0024]"

基金资助正文："<B>Funding</B> This work was supported by the National Nature Science Foundation of China (81703070) , Natural Science Foundation of Sichuan Province (2023NSFSC0708, 2020YJ0446) , and Beijing Xisike Clinical Oncology Research Foundation (Y-XD202001-0024) ."