Influence of CD47 on CD8+ T-cell and tumor prognosis based on pan-cancer analysis.

person Hongxin Liang Guangdong Cardiovascular Institute，Guangdong Provincial People's Hospital，Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China info_outline Hongxin Liang, Lintong Yao, Daipeng Xie, Hongrui Qiu, Zenan Lin, Hao Li, Jinhang Leng, Huili Wang, Xiuwei Jiao, Liyun Qiu, HaiYu Zhou

Authors person Hongxin Liang Guangdong Cardiovascular Institute，Guangdong Provincial People's Hospital，Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China info_outline Hongxin Liang, Lintong Yao, Daipeng Xie, Hongrui Qiu, Zenan Lin, Hao Li, Jinhang Leng, Huili Wang, Xiuwei Jiao, Liyun Qiu, HaiYu Zhou Organizations Guangdong Cardiovascular Institute，Guangdong Provincial People's Hospital，Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China, Department of Thoracic Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China, DepartmentofThoracicSurgery,GuangdongProvincialPeople'sHospital, Guangzhou, China, Guangzhou University of Chinese Medicine, Guangzhou, China, Southern Medical University, Guangzhou, China, Sun Yat-sen University Zhongshan School of Medicine, Guangzhou, China, Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China Abstract Disclosures Research Funding No funding received None. Background: CD47 was an immune checkpoint, constituting the CD47/SIRPα axis, sending the 'Do not eat me' signal to macrophages, hereby promoting immune escape of tumor cells in the tumor immune microenvironment(TIME). The role of CD47 has been proved affected immunotherapy efficacy and patient outcomes. However, how it affects TIME, specifically on CD8 + T-cell in pan-cancer, has not been fully illustrated. Therefore, we aimed to identify it, which could help us to gain insights into potential anti-cancer treatment. Methods: We used a lot of R package and computational tools to analysis of differential gene expression, prognosis, immunoinfiltration, pathway enrichment and Correlation. Single-cell sequencing and multiple immunofluorescence staining were uesd to verify our hypothesis. Data was based on 17,382 samples given by 948 healthy individuals from GTEx, 39 cancer types from TCGA, 79 databases and 2045746 cells from tumor patients and healthy donors in TISCH, and our real-world sample. Datasets were normalized for estimation of the TME components at both the single-cell and annotated cluster levels. Our study investigated the role of CD47 in prognosis and TIME, mainly from the view of adaptive immunity. Results: CD47 was expressed in nearly all cancer types, associated with worse prognosis in various cohorts in pan-cancer(p＜0.05) compared to the normal tissues. Then, we found CD47 was better correlated with tumor immune evasion through T-cell infiltration compared with T-cell rejection in multi-cancers. And we detected high CD47 expression with high CD8 + T-cell infiltration had a worse prognosis. So we hypothesis high CD47 could linked with T-cell exhausted. Then, we investigated that genetic alterations and oncogenic characteristics of CD47 were concomitant with the CD8 + T-cell exhausted by analysis of pathway and gene in mulit-cancer especially squamous-cell carcinomas. Finally, we proved CD47 synergy with CD8 + T-cell exhausted genes in LUSC and ESCA by single-cell analysis and multiple immune fluorescence staining. Conclusions: CD47 is highly associated with CD8 + T-cell exhausted and may induce cancer immune evasion leading to a worse prognosis. Thus, CD47 and T-cell exhausted correlated genes may serve as dual antigenic targets and provide insights into potential immunotherapy.

Pre-clinical