单位:[1]Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Peoples Republic of China华中科技大学同济医学院附属同济医院肿瘤生物医学中心[2]Department of Computer Science, City University of Hong Kong, Kowloon Tong, Hong Kong[3]Department of Biomedical Engineering, City University of Hong Kong, Kowloon Tong, Hong Kong
Treatment of ovarian cancer (OC) remains the biggest challenge among gynecological malignancies. Immune checkpoint blockade therapy is promising in many cancers but shows low response rates in OC because of its heterogeneity. Although the biological and molecular heterogeneity of OC has been extensively investigated, heterogeneity of immune microenvironment remains elusive. We have collected the expression profiles of 3071 OC patients from 22 publicly available datasets. CIBERSORT was applied to infer the infiltration fraction of 22 immune cells among 2086 patients with CIBERSORT P < .05. We then explored the heterogeneity landscape of immune microenvironment in OC at three levels (immune infiltration, prognostic relevance of immune infiltration, immune checkpoint expression patterns). Multivariable Cox regression model was used to investigate the associations between survival risk and immune infiltration. Constructed immune risk score stratified patients with significantly different survival risk (HR: 1.47, 95% CI: 1.31-1.66, P < .0001). The immune infiltration landscape, prognostic relevance of immune cells, and expression patterns of 79 immune checkpoints exhibited remarkable clinicopathological heterogeneity. For instance, M1 macrophages were significantly associated with better outcomes among patients with high-grade, late-stage, type-II OC (HR: 0.77-0.83), and worse outcomes among patients with type-I OC (HR: 1.78); M2 macrophages were significantly associated with worse outcomes among patients with high-grade, type-II OC (HR: 1.14-1.17); Neutrophils were significantly associated with worse outcomes among patients with high-grade, late-stage, type-I OC (HR: 1.14-1.73). The heterogeneous landscape of immune microenvironment presented in this study provided new insights into prognostic prediction and tailored immunotherapy of OC.
基金:
National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81772787]; National Key Research Development Program of China [2016YFC0902901]; Fundamental Research Funds for the Central UniversitiesFundamental Research Funds for the Central Universities [2017JYCXJJ025]
第一作者单位:[1]Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Peoples Republic of China
共同第一作者:
通讯作者:
通讯机构:[2]Department of Computer Science, City University of Hong Kong, Kowloon Tong, Hong Kong[*1]Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Anv., Wuhan, Peoples Republic of China
推荐引用方式(GB/T 7714):
gao yue,chen lingxi,cai guangyao,et al.Heterogeneity of immune microenvironment in ovarian cancer and its clinical significance: a retrospective study[J].ONCOIMMUNOLOGY.2020,9(1):doi:10.1080/2162402X.2020.1760067.
APA:
gao yue,chen lingxi,cai guangyao,xiong xiaoming,wu yuan...&gao qinglei.(2020).Heterogeneity of immune microenvironment in ovarian cancer and its clinical significance: a retrospective study.ONCOIMMUNOLOGY,9,(1)
MLA:
gao yue,et al."Heterogeneity of immune microenvironment in ovarian cancer and its clinical significance: a retrospective study".ONCOIMMUNOLOGY 9..1(2020)