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Selective Depletion of Tumor-Infiltrating CD4+CCR8+ Tregs by AZ084, a Novel CCR8 Antagonist

Yepeng Mao1,2, Ziqi Tao1,2, Shuna Liu1,2

  • 1Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.

Cancer Science
|July 12, 2026
PubMed

Insights

Regulatory T cells (Tregs) expressing CCR8 are key to ovarian cancer immunosuppression. Targeting CCR8 with AZ084 suppressed tumor growth and enhanced anti-tumor immunity with minimal systemic effects.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • Regulatory T cells (Tregs) mediate immunosuppression in ovarian cancer.
  • Targeting tumor-infiltrating Tregs remains a challenge.
  • CD4+CCR8+ Tregs are a proposed highly suppressive subset requiring functional validation.

Purpose of the Study:

  • To investigate the role of CCR8 in tumor-infiltrating Tregs.
  • To evaluate the therapeutic potential of targeting CCR8 in ovarian cancer and other models.
  • To assess the impact of CCR8 inhibition on anti-tumor immunity.

Main Methods:

  • Analysis of CCR8 expression on tumor-infiltrating T cells in ID8 and B16 tumor models.
  • In vitro assessment of CD4+CCR8+ Treg suppressive activity.
  • In vitro and in vivo evaluation of the CCR8 antagonist AZ084.
  • Flow cytometry analysis of immune cell populations in tumors and spleens.

Main Results:

  • CCR8 was preferentially expressed on tumor-infiltrating CD4+ Tregs compared to other T cell subsets.
  • CD4+CCR8+ Tregs demonstrated enhanced suppressive activity, inhibiting IFN-γ production by CD8+ T cells.
  • AZ084 impaired Treg differentiation, reduced Treg-mediated suppression in vitro, and suppressed tumor growth in vivo.
  • AZ084 treatment led to decreased tumor-infiltrating CD4+CCR8+ Tregs and increased CD8+ T cell infiltration and function.
  • AZ084 showed minimal impact on splenic immune cell composition, indicating limited systemic toxicity.

Conclusions:

  • CCR8 serves as a selective marker and functional regulator of tumor-infiltrating Tregs.
  • Targeting CCR8 with AZ084 is a promising strategy to enhance anti-tumor immunity.
  • AZ084 offers a potential therapeutic approach for ovarian cancer with preserved peripheral immune homeostasis.
Keywords:
AZ084CCR8chemokineovarian cancerregulatory T cells

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