@Article{biocell.2021.013882, AUTHOR = {MENGDAN WU, MENGYAO SUN, QINHUAI LAI, YIN LU, YUYIN FU, YUJIA PENG, WEIRONG LAI, LISHI ZENG, SHENGYAN ZHAO, YUYAN LI, ZHIXIONG ZHANG, XIAOFENG CHEN, FAN QIAO, YIWEN ZHANG, SHIJIE ZHOU,2, LANTU GOU, JINLIANG YANG,2}, TITLE = {Chemokine Ligand 13 Expression is Abundant in the Tumor Microenvironment and Indicates Poor Prognosis of Kidney Clear Cell Carcinoma}, JOURNAL = {BIOCELL}, VOLUME = {45}, YEAR = {2021}, NUMBER = {3}, PAGES = {589--597}, URL = {http://www.techscience.com/biocell/v45n3/41691}, ISSN = {1667-5746}, ABSTRACT = {The chemokine ligand 13-chemokine receptor 5 (CXCL13-CXCR5) axis has been characterized as a critical tumor-promoting signaling pathway in the tumor microenvironment (TME) in multiple types of solid tumors. In this study, we analyzed the expression profile of CXCL13 in kidney clear cell carcinoma (KIRC) and its correlation with tumor-infiltrating immune cells (TIICs). A monoclonal antibody against CXCL13 with high affinity and purity was generated in our lab for western blot and immunohistochemistry (IHC). Bioinformatic analysis was performed based on bulk-seq data from the Cancer Genome Atlas (TCGA)-KIRC and single-cell RNA-seq data from scRNASeqDB and PanglaoDB. Results showed that high CXCL13 expression in TME was associated with shorter progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). KIRC cell lines, as well as several other cancer cell lines, had negative CXCL13 expression. IHC staining from the Human Protein Atlas (HPA) and our tissue array indicated that CXCL13 might be mainly expressed by TIICs, but not KIRC tumor cells. CXCL13 expression was strongly and positively correlated with γδ T cell abundance in TME. Besides, γδ T cell infiltration was associated with poor survival of KIRC. Methylation 450k array data showed that CXCL13 promoter hypomethylation was common in TIICs. The methylation level of cg16361705 within the CXCL13 promoter might play an important role in modulating CXCL13 transcription. In conclusion, our study revealed that CXCL13 expression and γδ T cell infiltration in TME is associated with unfavorable survival of KIRC. TIICs, most possibly γδ T cells, are the dominant source of CXCL13 in KIRC TME.}, DOI = {10.32604/biocell.2021.013882} }