Combination therapy of HIFa inhibitors and Treg depletion strengthen the anti-tumor immunity in mice

作者全名："Wei, Ping; Kou, Wei; Riaz, Farooq; Zhang, Kaimin; Fu, Juan; Pan, Fan"

作者地址："[Wei, Ping; Kou, Wei] Chongqing Med Univ, Childrens Hosp, China Int Sci & Technol Cooperat base Child Dev &, Dept Otolaryngol,Minist Educ,Key Lab Child Dev & D, Chongqing, Peoples R China; [Riaz, Farooq; Zhang, Kaimin; Pan, Fan] Chinese Acad Sci, Shenzhen Inst Adv Technol SIAT, Shenzhen, Peoples R China; [Fu, Juan; Pan, Fan] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 21218 USA"

通信作者："Pan, F (通讯作者)，Chinese Acad Sci, Shenzhen Inst Adv Technol SIAT, Shenzhen, Peoples R China.; Pan, F (通讯作者)，Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 21218 USA."

来源：EUROPEAN JOURNAL OF IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001068257300001

JCR分区：Q2

影响因子：4.5

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Foxp3; Hypoxia-inducible factor 1 (HIF1 & alpha;); Regulatory T cells; CD8(+) T cells; Tumor immunity

摘要："Hypoxia-inducible factor 1 alpha (HIF1a), under hypoxic conditions, is known to play an oxygen sensor stabilizing role by exerting context- and cell-dependent stimulatory and inhibitory functions in immune cells. Nevertheless, how HIF1a regulates T cell differentiation and functions in tumor settings has not been elucidated. Herein, we demonstrated that T-cell-specific deletion of HIF1a improves the inflammatory potential and memory phenotype of CD8(+) T cells. We validated that T cell-specific HIF1a ablation reduced the B16 melanomas development with the indication of ameliorated antitumor immune response with enhanced IFN-?(+) CD8(+) T cells despite the increase in the Foxp3(+) regulatory T-cell population. This was further verified by treating tumor-bearing mice with a HIF1a inhibitor. Results indicated that HIF1a inhibitor also recapitulates HIF1a ablation effects by declining tumor growth and enhancing the memory and inflammatory potential of CD8(+) T cells. Furthermore, a combination of Treg inhibitor with HIF1a inhibitor can substantially reduce tumor size. Collectively, these findings highlight the notable roles of HIF1a in distinct CD8(+) T-cell subsets. This study suggests the significant implications for enhancing the potential of T cell-based antitumor immunity by combining HIF1a and Tregs inhibitors."

基金机构："National Key R&D Program of China [2022YFC2403000]; National Natural Science Foundation of China [32170925]; Shenzhen Science and Technology Program [KQTD20210811090115019, JCYJ2022081800807016]; SIAT and CAS; Natural Science Foundation of Chongqing Grant [CSTB2022NSCQ-MSX1069]; Chongqing for overseas Scholars Grant [CX2022118]"

基金资助正文："Fan Pan's work was supported by the National Key R&D Program of China (2022YFC2403000), the National Natural Science Foundation of China (Grant 32170925), Shenzhen Science and Technology Program (KQTD20210811090115019), the Shenzhen Science and Technology Program (JCYJ2022081800807016), the startup fund of SIAT and CAS. Ping Wei's work was supported by the Natural Science Foundation of Chongqing Grant CSTB2022NSCQ-MSX1069, the Chongqing for overseas Scholars Grant CX2022118."