Targeting LTA4H facilitates the reshaping of the immune microenvironment mediated by CCL5 and sensitizes ovarian cancer to Cisplatin

作     者：Zhengyang Guo Jiaqi Huang Xiao Huo Chen Huang Xiaotong Yu Yan Sun Yanfang Li Tianhui He Hongyan Guo Jianling Yang Lixiang Xue 

作者机构：Cancer Center of Peking University Third HospitalBeijing 100191China Center of Basic Medical ResearchInstitute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China Peking University Third Hospital Cancer CenterDepartment of Radiation OncologyPeking University Third HospitalBeijing 100191China Department of Obstetrics and GynecologyPeking University Third HospitalBeijing 100191China 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2024年第67卷第6期

页      面：1226-1241页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the General Program of National Natural Science Foundation of China(82272745,82072870,81972966) General Program of Natural Science Foundation of Beijing(7202224) the National Key Research and Development Program of China(2022YFA1104001) Youth Program of National Natural Science Foundation of China(82203102,82303801) Peking University Third Hospital Clinical Key Project(BYSY2022069)。 

主　　题：ovarian cancer polyunsaturated fatty acids prognostic risk model LTA4H tumor immunity CCL5 

摘      要：Ovarian cancer is the most lethal and aggressive gynecological cancer with a high recurrence rate and is often diagnosed late.In ovarian cancer,multiple metabolic enzymes of lipid metabolism are abnormally expressed,resulting in metabolism disorder.As a characteristic pathway in polyunsaturated fatty acid(PUFA)metabolism,arachidonic acid(AA)metabolism is disturbed in ovarian cancer.Therefore,we established a 10-gene signature model to evaluate the prognostic risk of PUFA-related genes.This 10-gene signature has strong robustness and can play a stable predictive role in datasets of various platforms(TCGA,ICGC,and GSE17260).The high association between the risk subgroups and clinical characteristics indicated a good performance of the model.Our data further indicated that the high expression of LTA4H was positively correlated with poor prognosis in ovarian cancer.Deficiency of LTA4H enhanced sensitivity to Cisplatin and modified the characteristics of immune cell infiltration in ovarian cancer.Additionally,our results indicate that CCL5 was involved in the aberrant metabolism of the AA/LTA4H axis,which contributes to the reduction of tumor-infiltrating CD8+T cells and immune escape in ovarian cancer.These findings provide new insights into the prognosis and potential target of LTA4H/CCL5 in treating ovarian cancer.