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Role of CXCR3 signaling in response to anti-PD-1 therapy

Xiao Han1, Ying Wang1, Jing Sun1

  • 1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

Ebiomedicine
|September 16, 2019
PubMed
Abstract

Insights

Peripheral CXCR3+ T cells indicate response to anti-PD-1 immunotherapy. High levels suggest progressive disease, while dynamic changes may predict treatment outcomes. Promoting CXCR3 signaling could enhance therapy effectiveness.

Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • Tumor mutations and microenvironment influence immunotherapy resistance.
  • Peripheral T cell roles in anti-programmed death 1 (PD-1) therapy are not fully understood.

Purpose of the Study:

  • To investigate the role of peripheral T cells, specifically CXCR3+ T cells, in anti-PD-1 antibody treatment response.
  • To explore the potential of CXCR3 signaling as a prognostic factor and therapeutic target in cancer immunotherapy.

Main Methods:

  • Mass spectrometry and flow cytometry analyzed peripheral blood cells from cancer patients.
  • A melanoma mouse model assessed the impact of CXCR3 signaling blockade and enhancement on anti-PD-1 therapy.

Main Results:

  • A significant increase in CXCR3+ T cells was observed after the first pembrolizumab infusion.
  • Sustained high levels of CXCR3+ T cells correlated with progressive disease, while decreasing levels indicated response.
  • Blocking CXCR3 signaling worsened tumor growth in mice, whereas CXCL9/10 plus anti-PD-1 inhibited tumor growth.

Conclusions:

  • Dynamic changes in peripheral CXCR3+ T cells may serve as a prognostic marker for anti-PD-1 immunotherapy.
  • Enhancing CXCR3-mediated signaling presents a potential strategy to improve anti-PD-1 therapy efficacy.
Keywords:
Anti-PD-1BiomarkerCXCR3Immunotherapy

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