Vaccination with CD47 deficient tumor cells elicits an antitumor immune response in mice

Yang Li1,2, Mingyou Zhang1,2, Xiaodan Wang1,3

  • 1Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital, and Institute of Immunology, Jilin University, Changchun, China.

Nature Communications
|January 31, 2020
PubMed

Insights

Eliminating CD47 from cancer cells enhances immune responses for vaccination. Combining CD47-deficient tumor cells with anti-PD-1 antibodies synergistically boosts antitumor immunity.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • Cancer cells often evade immune detection due to poor immunogenicity and high mutation rates.
  • Current cancer vaccination strategies face challenges in eliciting effective antitumor immune responses.

Purpose of the Study:

  • To investigate the impact of CD47 elimination on the immunogenicity of tumor cells.
  • To evaluate the efficacy of CD47-deficient tumor cell vaccination in established cancer models.
  • To explore combination therapies involving CD47 blockade and immune checkpoint inhibitors.

Main Methods:

  • Genetic deletion or antibody-mediated blocking of CD47 on mouse tumor cells.
  • Vaccination of tumor-bearing mice with CD47-deficient tumor cells or antigen-expressing cells.
  • Assessment of antitumor immune responses, including T cell activation and DC expansion.
  • Combination therapy with anti-PD-1 antibodies.

Main Results:

  • Elimination of CD47 significantly enhanced the immune response against tumor cells in both solid and hematopoietic mouse models.
  • Vaccination with CD47-deficient tumor cells induced a robust antitumor immune response.
  • The combination of CD47-deficient tumor cells and anti-PD-1 antibodies resulted in synergistic enhancement of efficacy.
  • CD47-deficient tumor cells promoted the expansion of SIRPα+CD11c+ dendritic cells, crucial for initiating antitumor immunity.

Conclusions:

  • CD47-deficient whole tumor cells can effectively induce antitumor immune responses.
  • Targeting CD47 represents a promising strategy to overcome tumor-induced immune suppression.
  • Combination therapy with CD47 blockade and PD-1 inhibitors offers a synergistic approach for cancer immunotherapy.

Related Concept Videos