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Potential Role of CXCL13/CXCR5 Signaling in Immune Checkpoint Inhibitor Treatment in Cancer

Ching-Hung Hsieh1, Cheng-Zhe Jian2, Liang-In Lin1

  • 1Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei City 10048, Taiwan.

Cancers
|January 21, 2022
PubMed

Insights

The CXCL13/CXCR5 signaling pathway is crucial for enhancing antitumor immune responses and improving the effectiveness of immune checkpoint inhibitors (ICIs) in cancer therapy. Targeting this axis shows promise for future cancer immunotherapy strategies.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, or CTLA-4 are major advances in cancer therapy.
  • CXC chemokine ligand 13 (CXCL13) binds CXC chemokine receptor type 5 (CXCR5), regulating adaptive immunity and tertiary lymphoid structure (TLS) formation.
  • CXCL13's role in ICI-responsive tumors is gaining attention as a prognostic and predictive factor.

Purpose of the Study:

  • To review how CXCL13/CXCR5 signaling influences cancer and immune cells.
  • To explore its role in promoting lymphocyte infiltration and activation against tumors.
  • To summarize preclinical and clinical evidence on targeting the CXCL13/CXCR5 axis for ICI therapy.

Main Methods:

  • Literature review of preclinical and clinical studies.
  • Analysis of the molecular mechanisms of CXCL13/CXCR5 signaling in cancer immunity.
  • Synthesis of data on the therapeutic implications of targeting this axis.

Main Results:

  • CXCL13/CXCR5 signaling promotes lymphocyte infiltration, tumor antigen activation, and differentiation, enhancing antitumor immunity.
  • Evidence suggests targeting the CXCL13/CXCR5 axis can improve responses to ICIs.
  • The pathway's role in TLS formation is linked to adaptive antitumor responses.

Conclusions:

  • The CXCL13/CXCR5 axis is a significant modulator of the antitumor immune response.
  • Targeting this pathway offers potential therapeutic strategies to enhance cancer immunotherapy efficacy.
  • Further research into CXCL13/CXCR5 signaling could lead to novel ICI-based treatments.
Keywords:
CXCL13/CXCR5immune checkpoint inhibitortertiary lymphoid structure

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