Table 1.
Cancer immunotherapy approaches related to the CXCL13/CXCR5 axis, based on preclinical models.
| Target in the Axis | Treatment | Disease | Experimental Method | Method of Detection | Value | Outcome |
|---|---|---|---|---|---|---|
| CXCR5+ CD8+ T cells | IL-21 Anti-PD-1 |
HBV-related HCC | Ex vivo from patients; in vivo in mice | RNA-seq qPCR IHC ELISA Western |
Favorable | CXCR5+CD8+ T cells are recruited to the liver, aiding antibody production and controlling the viral load. Anti-PD-1 and IL-21 treatment restore CXCR5+CD8+ T cell function [98]. |
| PD-1hi CXCL13+ CD39+CD4+ T cells | Anti-PD-1 | Head and neck cancer, cervical cancer, and ovarian cancer |
Ex vivo from patients | scRNA-Seq | Favorable | PD-1 blockade evokes CD39+CD4+ T cell function and improves dendritic cell maturation and CD8+ T cell proliferation [95]. |
| CXCL13+ immune cells | Anti-PD-1 CXCL13 | Ovarian cancer | In vivo in mice (subcutaneous) |
Immunofluorescence IHC ELISA |
Favorable | CXCL13 increases CD8+ T cell infiltration at the tumor site and upregulates effector cytokine levels. CXCL13 enhances the anti-PD-1 response [117]. |
| CXCR5+ CXCL13+ B cells | Anti-PD-1 Anti-CTLA4 |
Metastatic melanoma | Patients’ tumor samples | IHC Immunofluorescence |
Favorable | The co-occurrence of CD20+ B cells and CD8+ T cells is associated with better survival. Tertiary lymphoid structure formation containing CD8+ T cells and CD20+ B cells predicts clinical outcomes for immune checkpoint inhibitors [118]. |
| ID8 cells (cancer cells) secreting CXCL13 | Combination of CDK4/6i and anti-PD-1 | Ovarian cancer | In vivo in mice (ip) | RT Profiler PCR array | Favorable | CDK4/6 inhibition (abemaciclib) enhances CD8+ T cell, and B cell infiltration in a murine ovarian cancer model induces pro-inflammatory responses and increases CXCL13 secretion, which recruits additional lymphocytes to the tumor microenvironment. CDK4/6 inhibition and anti-PD-1 combination improve treatment efficacy in ovarian cancer [119]. |
| Cancer-associated fibroblasts expressing CXCL13 | Anti-PD-L1 Anti-CTLA4 |
Melanoma and colon adenocarcinoma | In vivo in mice (ip, subcutaneous) | Real-time PCR Immunofluorescence |
Favorable | Cancer-associated fibroblasts depend on tumor necrosis factor receptor signaling to orchestrate tumor-associated TLS development, and CD8+ T cells organize cancer-associated fibroblasts into reticular networks. The number and size of tumor-associated TLSs with discrete B and T cells are associated with favorable responses to immune checkpoint blockade [83]. |
CXCL, CXC chemokine ligand; PD-1, programmed cell death protein 1; CTLA4, cytotoxic T lymphocyte-associated protein 4; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; ip, intraperitoneal; RNA-seq, RNA-sequencing; qPCR, quantitative real-time reverse transcriptase-polymerase chain reaction; scRNA-seq, single-cell RNA-sequencing; IHC, immunohistochemistry; ELISA, enzyme-linked immunosorbent assay; TLS, tertiary lymphoid structure.