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<p>Type 1 conventional dendritic cells (cDC1s) are key antigen-presenting cells (APCs) for cross-priming of CD8<sup>+</sup> T cells against cancer. They can capture and cross-present dead cell antigens via DNGR-1 (CLEC9A), a receptor for F-actin exposed on cell corpses. However, cDC1s are scarce in human and murine tumors, and this restricts anticancer immunity. We show that abundant tumor-associated APCs, including cDC2s and monocyte-derived cells, can be redirected to internalize necrotic debris and cross-present associated antigens by a variety of reagents that bridge F-actin to Fcγ receptors (FcγRs), including an Fc–DNGR-1 fusion protein and an anti-F-actin antibody. In vivo, Fc–DNGR-1 accumulates in necrotic tumor areas and highlights their proximity to intratumoral FcγR<sup>+</sup> APCs. In mouse cancer models, F-actin–FcγR bridging enhances tumor control and synergizes with cytotoxic chemotherapy or radiotherapy. Thus, nonspecialized APCs can be harnessed for cross-presentation of necrotic tumor antigens, and F-actin–FcγR bridging constitutes a strategy to potentiate anticancer immunity.</p>

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Coupling dead cell recognition to Fcγ receptors augments anticancer immunity

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月20日

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  • Tomás Castro-Dopico,
  • Cécile Piot,
  • Michael D. Buck,
  • Lucía Gandullo-Sánchez,
  • Kok Haw Jonathan Lim,
  • Gerone A. Gonzales,
  • Nikita Rosendahl,
  • Oliver Schulz,
  • William Stainier,
  • Brian Vash,
  • Stephanie Maiocco,
  • Conor M. Henry,
  • Bruno Frederico,
  • Sonia Lee,
  • Andy Bo Zhang,
  • Neil C. Rogers,
  • Jayanta Bordoloi,
  • Chloë Roustan,
  • Svend Kjaer,
  • Mohit Trikha,
  • Hans Stauss,
  • Ahmet Hazini,
  • Kristen J. Radford,
  • Zewen Kelvin Tuong,
  • Johnathan Canton,
  • Raj Mehta,
  • Caetano Reis e Sousa

摘要

Type 1 conventional dendritic cells (cDC1s) are key antigen-presenting cells (APCs) for cross-priming of CD8+ T cells against cancer. They can capture and cross-present dead cell antigens via DNGR-1 (CLEC9A), a receptor for F-actin exposed on cell corpses. However, cDC1s are scarce in human and murine tumors, and this restricts anticancer immunity. We show that abundant tumor-associated APCs, including cDC2s and monocyte-derived cells, can be redirected to internalize necrotic debris and cross-present associated antigens by a variety of reagents that bridge F-actin to Fcγ receptors (FcγRs), including an Fc–DNGR-1 fusion protein and an anti-F-actin antibody. In vivo, Fc–DNGR-1 accumulates in necrotic tumor areas and highlights their proximity to intratumoral FcγR+ APCs. In mouse cancer models, F-actin–FcγR bridging enhances tumor control and synergizes with cytotoxic chemotherapy or radiotherapy. Thus, nonspecialized APCs can be harnessed for cross-presentation of necrotic tumor antigens, and F-actin–FcγR bridging constitutes a strategy to potentiate anticancer immunity.