Cryoablation triggers type I interferon-dependent antitumor immunity and potentiates immunotherapy efficacy in lung cancer

doi:10.1136/jitc-2023-008386

	Cryoablation triggers type I interferon-dependent antitumor immunity and potentiates immunotherapy efficacy in lung cancer
	Gu, Chuanjia 1,2,3; Wang, Xue 4; Wang, Kaiyu 4,5; Xie, Fangfang 1,2,3; Chen, Luonan4,5,6,7,8 ; Ji, Hongbin4,5,6,7 ; Sun, Jiayuan 1,2,3
	2024
发表期刊	JOURNAL FOR IMMUNOTHERAPY OF CANCER
EISSN	2051-1426
卷号	12 期号:1
发表状态	已发表
DOI	10.1136/jitc-2023-008386
摘要	Background Cryoablation is a minimally invasive option for patients with medically inoperable non-small cell lung cancer (NSCLC) and can trigger abscopal immune-regulatory effects. However, it remains unclear how cryoablation affects the host-level immune response in NSCLC. In this study, we investigated the local and systemic immunological effects of cryoablation and the potential of combining cryoablation with programmed cell death protein 1 (PD-1) blockade to boost immunotherapy efficacy in NSCLC.Methods We first investigated systemic immunological effects induced by cryoablation in patients with early-stage NSCLC. Subsequently, we explored cryoablation-induced antitumor immunity and the underlying biological mechanisms using KP (Kras G12D/+, Tp53 -/-) mutant lung cancer cell allograft mouse models. Moreover, the synergistic efficacy of cryoablation and PD-1 blockade was explored in both mouse models and patients with unresectable NSCLC.Results We found that cryoablation significantly increased circulating CD8+ T cell subpopulations and proinflammatory cytokines in patients with early-stage NSCLC. In lung cancer cell allograft mouse models, we demonstrated that cryoablation resulted in abscopal growth inhibition of contralateral, non-ablated tumors. Integrated analysis of bulk, single-cell RNA and T cell receptor (TCR) sequencing data revealed that cryoablation reprogrammed the intratumoral immune microenvironment and increased CD8+ T cell infiltration with higher effector signature, interferon (IFN) response, and cytolytic activity. Mechanistically, cryoablation promoted antitumor effect through the STING-dependent type I IFN signaling pathway, and type I IFN signaling blockade attenuated this antitumor effect. We also found that the combination of PD-1 blockade with cryoablation further inhibited tumor growth compared with either treatment alone in an allograft mouse model. Moreover, the combination therapy induced notable tumor suppression and CD8+ T cell infiltration in patients with unresectable NSCLC.Conclusions Our results provide mechanistic insights into how cryoablation triggers the antitumor immune effect in lung cancer, thereby potentiating programmed cell death ligand 1 (PD-L1)/PD-1 blockade efficacy in the clinical treatment of NSCLC.
关键词	immunotherapy non-small cell lung cancer immune checkpoint inhibitors tumor microenvironment
URL	查看原文
收录类别	SCI
语种	英语
资助项目	Nurture Projects for Basic Research of Shanghai Chest Hospital["2021YNJCQ4","2019YNJCM10"] ; National Multi- disciplinary Treatment Project for Major Diseases[2020NMDTP]
WOS研究方向	Oncology ; Immunology
WOS类目	Oncology ; Immunology
WOS记录号	WOS:001153905700008
出版者	BMJ PUBLISHING GROUP
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/349935
专题	生命科学与技术学院生命科学与技术学院_特聘教授组_季红斌组生命科学与技术学院_特聘教授组_陈洛南组
通讯作者	Sun, Jiayuan
作者单位	1.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Dept Resp Endoscopy, Sch Med, Shanghai, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, Shanghai Chest Hosp, Dept Resp & Crit Care Med, Shanghai, Peoples R China 3.Shanghai Engn Res Ctr Resp Endoscopy, Shanghai, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol, Shanghai, Peoples R China 5.Univ Chinese Acad Sci, Beijing, Peoples R China 6.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 7.Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci,Key Lab Syst Hlth Sci Zhejiang Prov, Hangzhou, Peoples R China 8.Guangdong Inst Intelligence Sci & Technol, Hengqin, Zhuhai, Guangdong, Peoples R China
推荐引用方式 GB/T 7714	Gu, Chuanjia,Wang, Xue,Wang, Kaiyu,et al. Cryoablation triggers type I interferon-dependent antitumor immunity and potentiates immunotherapy efficacy in lung cancer[J]. JOURNAL FOR IMMUNOTHERAPY OF CANCER,2024,12(1).
APA	Gu, Chuanjia.,Wang, Xue.,Wang, Kaiyu.,Xie, Fangfang.,Chen, Luonan.,...&Sun, Jiayuan.(2024).Cryoablation triggers type I interferon-dependent antitumor immunity and potentiates immunotherapy efficacy in lung cancer.JOURNAL FOR IMMUNOTHERAPY OF CANCER,12(1).
MLA	Gu, Chuanjia,et al."Cryoablation triggers type I interferon-dependent antitumor immunity and potentiates immunotherapy efficacy in lung cancer".JOURNAL FOR IMMUNOTHERAPY OF CANCER 12.1(2024).