Prognostic impact and landscape of cellular CXCR5 chemokine receptor expression in clear-cell renal cell carcinoma.

CXCR5 is a chemokine receptor that promotes B cell follicular formation and antibody production. Indeed, CXCR5 has been found to be expressed in a variety of cancers; however, the role of CXCR5 expression in clear-cell renal cell carcinoma (ccRCC) remains unclear. We aimed to determine the impact of cellular CXCR5 expression on cancer outcomes, the PD-1/PD-L1 axis, and genetic states in patients with ccRCC. First, multiplex immunofluorescence staining for CXCR5, CD4, CD8, and AE1/AE3, along with automated single-cell counting, was performed to assess cellular CXCR5 expression in ccRCC and its association with prognosis. Second, the tumour microenvironment (TME) was analysed, with a focus on the relationship between the PD-1/PD-L1 axis and CXCR5 expression. Finally, an integrated analysis of CXCR5 expression and genomic mutation information was conducted to reveal the genetic background underlying CXCR5 expression. A total of 105 ccRCC patients were included. Among the 696,964 cells analysed, the distribution of CXCR5-expressing cells was as follows: 30% CXCR5⁺CD4⁺ cells, 9% CXCR5⁺CD8⁺ cells, and 26% CXCR5⁺AE1/AE3⁺ cells. Survival analysis revealed that tumours with low-CXCR5⁺CD8⁺ cells had a poor prognosis; TME analysis revealed a relationship between low-CXCR5⁺CD8⁺ status and a highly suppressive PD-L1-positive immune environment. Genomic analysis revealed a correlation between low-CXCR5⁺CD8⁺ status and high rates of alterations in chromatin remodelling genes, including PBRM1. This study highlights the significance of CXCR5⁺CD8⁺ cells in ccRCC, demonstrating their clinical implications and revealing the immunogenomic landscape underlying CXCR5 expression.