CXCL13

CXCL13 is a small chemokine belonging to the CXC chemokine family. As its other names suggest, this chemokine is selectively chemotactic for B cells belonging to both the B-1 and B-2 subsets, and elicits its effects by interacting with chemokine receptor CXCR5. CXCL13 and its receptor CXCR5 control the organization of B cells within follicles of lymphoid tissues and is expressed highly in the liver, spleen, lymph nodes, and gut of humans. The gene for CXCL13 is located on human chromosome 4 in a cluster of other CXC chemokines.

In T lymphocytes, CXCL13 expression is thought to reflect a germinal center origin of the T cell, particularly a subset of T cells called follicular B helper T cells (or T_FH cells). Hence, expression of CXCL13 in T-cell lymphomas, such as angioimmunoblastic T-cell lymphoma, is thought to reflect a germinal center origin of the neoplastic T-cells.

The chemokine CXCL13 plays a dual and context-dependent role in cancer progression and the efficacy of treatments. Within the tumor microenvironment (TME), it is essential for the organization of tertiary lymphoid structures (TLS), which act as hubs for local immune activation and are typically associated with a favorable prognosis and better response to immunotherapy. In contrast, elevated systemic levels of CXCL13 in the plasma have been identified as a significant biomarker of primary resistance to immunotherapy and poor clinical outcomes, especially in non-small cell lung cancer (NSCLC). High circulating levels of CXCL13 often reflect a dysregulated peripheral immune profile characterized by cytotoxic T cell exhaustion (indicated by increased markers such as LAG3 and PD-L1) and impaired B-cell maturation, which together limit the immune system's ability to respond effectively to therapy.