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

• Published in: Life (Basel, Switzerland) Vol. 13; no. 2; p. 553
• Main Authors: Hoellwerth, Magdalena, Koelblinger, Peter, Lang, Roland, Harrer, Andrea
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2023; MDPI
• Subjects: Analysis; anti-PD-1 therapy; Antibodies; Antigens; Biological markers; biomarker; Biomarkers; Blood circulation; Care and treatment; Cell migration; CXCL13; CXCL13 protein; CXCR5; CXCR5 protein; Cytokines; Dendritic cells; Diagnosis; Effector cells; Follicles; Health aspects; Helper cells; Immune checkpoint inhibitors; Immunology; Immunotherapy; Inflammation; Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes B; Lymphocytes T; Melanoma; Metastasis; Monoclonal antibodies; PD-1 protein; Review; Skin cancer; TLS; Tumors; Austria; CXCR5; melanoma; TLS; CXCL13; anti-PD-1 therapy; biomarker
• ISSN: 2075-1729; 2075-1729
• DOI: 10.3390/life13020553

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.