Innate immune checkpoint Siglec10 in cancers: mining of comprehensive omics data and validation in patient samples.
10.1007/s11684-021-0868-z
- Author:
Chen ZHANG
1
;
Jiandong ZHANG
2
;
Fan LIANG
1
;
Han GUO
1
;
Sanhui GAO
1
;
Fuying YANG
1
;
Hua GUO
3
;
Guizhen WANG
3
;
Wei WANG
4
;
Guangbiao ZHOU
5
Author Information
1. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing, 100101, China.
2. Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.
3. State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
4. Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China. weiwang0920@163.com.
5. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences & University of Chinese Academy of Sciences, Beijing, 100101, China. gbzhou@cicams.ac.cn.
- Publication Type:Journal Article
- Keywords:
Siglec10;
innate immune checkpoint;
kidney renal clear cell carcinoma
- MeSH:
Carcinoma, Renal Cell/pathology*;
Gene Expression Regulation, Neoplastic;
Humans;
Immunity, Innate;
Kidney Neoplasms/pathology*;
Lectins/metabolism*;
Prognosis;
Receptors, Cell Surface/metabolism*
- From:
Frontiers of Medicine
2022;16(4):596-609
- CountryChina
- Language:English
-
Abstract:
Sialic acid binding Ig-like lectin 10 (Siglec10) is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells. Here, by analyzing public databases containing 64 517 patients of 33 cancer types, we found that the expression of Siglec10 was altered in 18 types of cancers and was associated with the clinical outcomes of 11 cancer types. In particular, Siglec10 was upregulated in patients with kidney renal clear cell carcinoma (KIRC) and was inversely associated with the prognosis of the patients. In 131 KIRC patients of our settings, Siglec10 was elevated in the tumor tissues of 83 (63.4%) patients compared with that in their counterpart normal kidney tissues. Moreover, higher level of Siglec10 was associated with advanced disease (stages III and IV) and worse prognosis. Silencing of CD24 in KIRC cells significantly increased the number of Siglec10-expressing macrophages phagocytosing KIRC cells. In addition, luciferase activity assays suggested that Siglec10 was a potential target of the transcription factors c-FOS and GATA1, which were identified by data mining. These results demonstrate that Siglec10 may have important oncogenic functions in KIRC, and represents a novel target for the development of immunotherapies.
