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Radiotherapy-exposed CD8+ and CD4+ neoantigens enhance tumor control

Claire Lhuillier1, Nils-Petter Rudqvist1, Takahiro Yamazaki1

  • 1Department of Radiation Oncology and.

The Journal of Clinical Investigation
|January 21, 2021
PubMed

Insights

Radiotherapy enhances cancer vaccines by increasing neoantigen presentation. Neoantigen vaccination combined with radiotherapy boosts T cell responses and improves tumor control in preclinical models.

Area of Science:

  • Immunology
  • Cancer Biology
  • Radiotherapy

Background:

  • Neoantigens are crucial for T cell recognition of cancer, but their presentation and therapeutic efficacy are often limited.
  • Existing neoantigen vaccination strategies show suboptimal antitumor activity due to incompletely understood mechanisms.

Purpose of the Study:

  • To investigate the synergistic effects of radiotherapy and neoantigen vaccination in a triple-negative breast cancer model.
  • To elucidate the mechanisms by which neoantigen vaccination enhances radiotherapy's therapeutic efficacy.

Main Methods:

  • Utilized a poorly immunogenic mouse model of triple-negative breast cancer.
  • Administered radiotherapy and vaccinated with neoepitopes derived from upregulated immunogenic mutation genes.
  • Assessed T cell responses (CD8+ and CD4+), tumor growth, and therapeutic efficacy.

Main Results:

  • Radiotherapy upregulated genes with immunogenic mutations, enhancing neoantigen presentation.
  • Neoepitope vaccination elicited CD8+ and CD4+ T cell responses, which improved radiotherapy efficacy.
  • Neoantigen-specific CD8+ T cells killed irradiated tumor cells; CD4+ T cells promoted tumor killing and epitope spread via Th1 cytokines.

Conclusions:

  • Radiotherapy and neoantigen vaccination act synergistically to improve tumor control.
  • Radiotherapy enhances the immunogenicity of cancer by upregulating MHC class II and death receptors on tumor cells, sensitizing them to neoantigen-specific T cells.
Keywords:
AntigenBreast cancerImmunologyOncologyRadiation therapy

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