A Novel Prognostic Biomarker CCR8 for Gastric Cancer and Anti-CCR8 Blockade Attenuate the Immunosuppressive Capacity of Tregs In Vitro

Cancer Biother Radiopharm. 2023 Aug;38(6):415-424. doi: 10.1089/cbr.2022.0095. Epub 2023 Apr 26.

Abstract

Objective: To investigate the immunotherapeutic roles and functions of C-C Motif Chemokine Receptor 8 (CCR8) molecule in gastric cancer (GC). Materials and Methods: Clinicopathological features of 95 GC cases were collected by a follow-up survey. The expression level of CCR8 was measured by immunohistochemistry (IHC) staining and analyzed with the cancer genome atlas database. The relationship between CCR8 expression and Clinicopathological features of GC cases was evaluated by univariate and multivariate analysis. Flow cytometry was used to determine the expression of cytokines and the proliferation of CD4+ regulator T cells (Tregs) and CD8+ T cells. Results: An upregulated expression of CCR8 in GC tissues was associated with tumor grade, nodal metastasis, and overall survival (OS). Tumor-infiltrated Tregs with higher expression of CCR8 produced more IL10 molecules in vitro. In addition, anti-CCR8 blocking downregulated IL10 expression produced by CD4+ Tregs, and reversed the suppression by Tregs on the secretion and proliferation of CD8+ T cells. Conclusion: CCR8 molecule could be a prognostic biomarker for GC cases and a therapeutic target for immune treatments.

Keywords: CCR8; gastric cancer; immunotherapy; prognosis; regulatory T cell.

MeSH terms

  • Biomarkers / metabolism
  • CD8-Positive T-Lymphocytes* / metabolism
  • Humans
  • Interleukin-10 / metabolism
  • Prognosis
  • Receptors, CCR8 / metabolism
  • Receptors, Chemokine / metabolism
  • Stomach Neoplasms* / metabolism
  • T-Lymphocytes, Regulatory

Substances

  • Receptors, Chemokine
  • Interleukin-10
  • Biomarkers
  • CCR8 protein, human
  • Receptors, CCR8