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Co-targeting CD47 and VEGF elicited potent anti-tumor effects in gastric cancer

Kaiqi Zhang1, Yuan Xu1, Xusheng Chang1

  • 1Department of Gastrointestinal Surgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.

Cancer Immunology, Immunotherapy : CII
|March 27, 2024
PubMed
Abstract

Insights

High CD47 expression in gastric cancer correlates with poor prognosis. Targeting CD47 with immunotherapy, combined with anti-angiogenic therapy, shows promise for treating gastric cancer by enhancing phagocytosis and prolonging survival.

Area of Science:

  • Oncology
  • Immunotherapy
  • Cancer Biology

Background:

  • CD47 is an immune checkpoint effective in hematologic malignancies.
  • The role of CD47 in gastric cancer (GC) and its therapeutic potential are not well understood.

Purpose of the Study:

  • To investigate the expression and prognostic significance of CD47 in gastric cancer.
  • To evaluate the efficacy of anti-CD47 immunotherapy, alone and in combination with anti-angiogenic therapy, in preclinical gastric cancer models.

Main Methods:

  • Immunohistochemistry and Western blot to assess CD47 expression in GC tissues.
  • In vitro co-culture assays with patient-derived cells and macrophages to evaluate phagocytosis.
  • Humanized patient-derived xenografts (Hu-PDXs) models to test anti-CD47 and anti-VEGF therapies.
  • Flow cytometry and immunohistochemistry for analyzing phagocytosis and immune cell infiltration.

Main Results:

  • CD47 is highly expressed in GC tissues and associated with unfavorable prognosis.
  • Anti-CD47 therapy (SIRPα-Fc) enhanced macrophage phagocytosis and inhibited Hu-PDX growth.
  • Combined anti-CD47 and anti-angiogenic therapy (anti-VEGF) demonstrated superior anti-tumor efficacy, suppressed tumor growth, prevented recurrence, and prolonged survival in Hu-PDX models.
  • A positive correlation between VEGF and CD47 expression in GC was observed.

Conclusions:

  • CD47 is a promising therapeutic target for gastric cancer.
  • Anti-angiogenic therapy can enhance the efficacy of anti-CD47 immunotherapy in gastric cancer.
Keywords:
Angiogenic vasculatureAnti-CD47 therapyCombinational therapyInnate immunityVEGF

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