Background C-X-C motif chemokine ligand 13 (CXCL13) is a crucial chemokine for the recruitment of immune cells and the formation of tertiary lymphoid structure (TLS) in the tumor microenvironment. However, the relationship between CXCL13 and immune infiltration in cutaneous squamous cell carcinoma (cSCC) remains unclear. Objective We aimed to investigate the expression of CXCL13 and explore its association with immune activation and TLS in cSCC. Methods A total of 63 cSCC patients were involved in the present study. Hematoxylin and eosin staining was used for pathological examination of cSCC. Bioinformatics analyses and immunohistochemical staining were employed to access the expression of CXCL13 and TLS states. Public single cell RNA-sequencing atlas of skin disorders and multiplex immunofluorescence were used to explore CXCL13-producing cells. Results Utilizing the public database and our clinical cohort, we observed robust CXCL13 expression in cSCC tissues and a significant correlation with immune activation. Higher expression levels of CXCL13 were associated with lower histopathological grades and increased TLS formation. Furthermore, we confirmed that T cells and fibroblasts were the predominant cell types of CXCL13 secretion in cSCC. Conclusions CXCL13 is up-regulated in cSCC, which shows a significant positive correlation with immune infiltration and TLS formation. Our results underscore the role of CXCL13 in shaping the cSCC microenvironment, highlighting its potential as a therapeutic target.
