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Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells
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Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells

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Type 2 dendritic cells mediate control of cytotoxic T cell resistant tumors

Stephen Iwanowycz1, Soo Ngoi2, Yingqi Li1

  • 1Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina (MUSC), Charleston, South Carolina, USA.

JCI Insight
|July 20, 2021
PubMed

Insights

Type 2 dendritic cells (DC2s) are crucial for antitumor immunity, especially in tumors resistant to T cell attacks. Enhancing DC2 function improves immune response and survival in breast cancer models.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • Type 2 dendritic cells (DC2s) are the predominant conventional dendritic cell type in tumors.
  • Their role in initiating and sustaining antitumor immunity is largely unexplored, with research focus on DC1s.
  • DC2s show prognostic potential in human cancers, particularly in tumors resistant to cytotoxic T cell-mediated control.

Purpose of the Study:

  • To investigate the role of DC2s in antitumor immunity.
  • To explore the therapeutic potential of DC2s in immunotherapy-resistant cancers.
  • To understand the mechanisms by which DC2s influence T cell responses and tumor control.

Main Methods:

  • Analysis of human cancer datasets to correlate DC2 infiltration with patient survival.
  • Utilizing mouse models of immunotherapy-resistant breast cancer.
  • Employing BATF3-deficient models to deplete DC1s and assess DC2 functionality.
  • Genetic deletion of Hsp90b1 to enhance DC2 stimulatory potential.

Main Results:

  • DC2 infiltration correlates with improved survival across multiple human cancers, especially in tumors resistant to cytotoxic T cells.
  • Impairment of DC1s enhances DC2 functionality, leading to improved tumor control in breast cancer models.
  • BATF3 deficiency increases DC2 lymph node migration and CD4+ T cell activation.
  • Enhancing DC2 stimulatory potential improves T cell immunity and survival in a spontaneous breast cancer model.

Conclusions:

  • DC2s possess significant therapeutic and prognostic potential in checkpoint blockade-resistant tumors.
  • Modulating DC2 function represents a promising strategy for enhancing antitumor immunity.
  • DC2s play a critical role in overcoming resistance to T cell-mediated therapies.
Keywords:
Breast cancerChaperonesDendritic cellsImmunology

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