Revisiting the Role of the CXCL13/CXCR5-Associated Immune Axis in Melanoma: Potential Implications for Anti-PD-1-Related Biomarker Research

CXCL13 is a potent chemoattractant cytokine that promotes the migration of cells expressing its cognate receptor, CXCR5. Accordingly, T follicular helper cells and B cells migrate towards B cell follicles in lymph nodes, where the resulting spatial proximity promotes B cell/T cell interaction and antibody formation. Moreover, effector cells of the CXCL13/CXCR5-associated immune axis express PD-1, with corresponding circulating cells occurring in the blood. The formation of so-called ectopic or tertiary lymphoid structures, recently detected in different cancer types, represents an integral part of this axis, particularly in the context of its emerging role in anti-tumor defense. These aspects of the CXCL13/CXCR5-associated immune axis are highlighted in this review, which focuses on cutaneous malignant melanoma. Specifically, we elaborate on the role of this important immune axis as a possible ancillary target of immune checkpoint inhibition with anti-PD-1 antibodies in different therapeutic settings and as a potential source of predictive biomarkers regarding treatment efficacy.

Automated summary

CXCL13 is a potent cytokine that attracts cells expressing its receptor, CXCR5, and promotes their migration. This leads to the migration of T follicular helper cells and B cells towards B cell follicles in lymph nodes, facilitating B cell/T cell interaction and antibody formation. The CXCL13/CXCR5-associated immune axis is also associated with the expression of PD-1 in effector cells and the occurrence of corresponding circulating cells. Ectopic or tertiary lymphoid structures detected in different cancer types are an integral part of this immune axis and have implications in anti-tumor defense.