Tozasertib activates anti-tumor immunity through decreasing regulatory T cells in melanoma

作者全名："Wang, Qiaoling; Liu, Wuyi; Zhou, Huyue; Lai, Wenjing; Hu, Changpeng; Dai, Yue; Li, Guobing; Zhang, Rong; Zhao, Yu"

作者地址："[Wang, Qiaoling; Zhao, Yu] Chongqing Med Univ, Univ Town Hosp, Dept Pharm, Chongqing, Peoples R China; [Liu, Wuyi; Zhou, Huyue; Lai, Wenjing; Hu, Changpeng; Dai, Yue; Li, Guobing; Zhang, Rong] Army Med Univ, Dept Pharm, Affiliated Hosp 2, Chongqing, Peoples R China"

通信作者："Zhao, Y (通讯作者)，Chongqing Med Univ, Univ Town Hosp, Dept Pharm, Chongqing, Peoples R China.; Zhang, R (通讯作者)，Army Med Univ, Dept Pharm, Affiliated Hosp 2, Chongqing, Peoples R China."

来源：NEOPLASIA

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001167977200001

JCR分区：Q1

影响因子：6.3

年份：2024

卷号：48

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Aurora kinase; Immune checkpoint; Immune infiltration; Single-cell analysis; Tumor microenvironment

摘要："Although immune checkpoint therapy has significantly improved the prognosis of patients with melanoma, urgent attention still needs to be paid to the low patient response rates and the challenges of precisely identifying patients before treatment. Therefore, it is crucial to investigate novel immunosuppressive mechanisms and targets in the tumor microenvironment in order to reverse tumor immune escape. In this study, we found that the cell cycle checkpoint Aurora kinase B (AURKB) suppressed the anti -tumor immune response, and its inhibitor, Tozasertib, effectively activated T lymphocyte cytokine release in vitro and anti -tumor immunity in vivo. Tozasertib significantly inhibited melanoma xenograft tumor growth by decreasing the number of inhibitory CD4+ Treg cells in the tumors, which, in turn, activated CD8+ T cells. Single-cell analysis revealed that AURKB suppressed anti -tumor immunity by increasing MIF-CD74/CXCR4 signaling between tumor cells and lymphocytes. Our study suggests that AURKB is a newly identified anti -tumor immunity suppressor, whose inhibitors may be developed as novel anti -tumor immunity drugs and may have synergistic anti-melanoma effects with immune checkpoint therapies."

基金机构：National Natural Science Foundation of China [82104453]; Red Medical Famous teacher of Army Medical University; Red Medical Talent Project of Army Medical University; Chongqing Key Specialty Construction Project of Clinical Pharmacy (Clinical Pharmacy of Medical oncology)

基金资助正文：This work was supported by National Natural Science Foundation of China (82104453) ; the Red Medical Famous teacher of Army Medical University (Rong Zhang) ; the Red Medical Talent Project of Army Medical University (Wuyi Liu) and the Chongqing Key Specialty Construction Project of Clinical Pharmacy (Clinical Pharmacy of Medical oncology) .