S100A16 is a potential target for reshaping the tumor microenvironment in the hypoxic context of liver cancer

Dashuai Yang; Fangrui Zhao; Yu Zhou; Yanbing Zhang; Jie Shen; Bin Yu; Kailiang Zhao; Youming Ding

doi:10.1016/j.intimp.2024.112076

S100A16 is a potential target for reshaping the tumor microenvironment in the hypoxic context of liver cancer

Int Immunopharmacol. 2024 May 10:134:112076. doi: 10.1016/j.intimp.2024.112076. Online ahead of print.

Authors

Dashuai Yang¹, Fangrui Zhao², Yu Zhou¹, Yanbing Zhang¹, Jie Shen¹, Bin Yu¹, Kailiang Zhao³, Youming Ding⁴

Affiliations

¹ Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuchang District, Wuhan 430060, China.
² Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 Hubei Province, China.
³ Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuchang District, Wuhan 430060, China. Electronic address: zhaokl1983@qq.com.
⁴ Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuchang District, Wuhan 430060, China. Electronic address: dingym@whu.edu.cn.

PMID: 38733818
DOI: 10.1016/j.intimp.2024.112076

Abstract

Background: The research on the S100 family has garnered significant attention; however, there remains a dearth of understanding regarding the precise role of S100A16 in the tumor microenvironment of liver cancer.

Method: Comprehensive analysis was conducted on the expression of S100A16 in tumor tissues and its correlation with hypoxia genes. Furthermore, an investigation was carried out to examine the association between S100A16 and infiltration of immune cells in tumors as well as immunotherapy. Relevant findings were derived from the analysis of single cell sequencing data, focusing on the involvement of S100A16 in both cellular differentiation and intercellular communication. Finally, we validated the expression of S100A16 in liver cancer by Wuhan cohort and multiplexed immunofluorescence to investigate the correlation between S100A16 and hypoxia.

Result: Tumor tissues displayed a notable increase in the expression of S100A16. A significant correlation was observed between S100A16 and genes associated with hypoxic genes. Examination of immune cell infiltration revealed an inverse association between T cell infiltration and the level of S100A16 expression. The high expression group of S100A16 exhibited a decrease in the expression of genes related to immune cell function. Single-cell sequencing data analysis revealed that non-immune cells predominantly expressed S100A16, and its expression levels increased along with the trajectory of cell differentiation. Additionally, there were significant variations observed in hypoxia genes as cells underwent differentiation. Cellular communication identified non-immune cells interacting with immune cells through multiple signaling pathways. The Wuhan cohort verified that S100A16 expression was increased in liver cancer. The expression of S100A16 and HIF was simultaneously elevated in endothelial cells.

Conclusion: The strong association between S100A16 and immune cell infiltration is observed in the context of hypoxia, indicating its regulatory role in shaping the hypoxic tumor microenvironment in liver cancer.

Keywords: Hypoxia; Immunotherapy; Liver cancer; S100A16; Tumor microenvironment.