pDC depletion induced by CD317 blockade drives the antitumor immune response in head and neck squamous cell carcinoma

Lei-Lei Yang1, Liang Mao1, Hao Wu1

  • 1The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei- MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Wuhan, China.

Oral Oncology
|August 19, 2019
PubMed
Abstract

Insights

Depleting plasmacytoid dendritic cells (pDCs) in head and neck squamous cell carcinoma (HNSCC) models delayed tumor growth and improved T cell function. High pDC infiltration in human HNSCC correlates with poor prognosis, suggesting pDCs as a potential immunotherapy target.

Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • Immune cell dysregulation in the tumor microenvironment is characteristic of head and neck squamous cell carcinoma (HNSCC).
  • Increased infiltration of plasmacytoid dendritic cells (pDCs) has been observed in HNSCC, but their exact role and therapeutic potential remain unclear.

Purpose of the Study:

  • To investigate the immunological role of pDCs in HNSCC.
  • To evaluate the therapeutic effects of pDC depletion in HNSCC models.
  • To analyze the prognostic significance of pDC infiltration in human HNSCC.

Main Methods:

  • Utilized CD317 antibodies for pDC depletion in a transgenic HNSCC mouse model.
  • Monitored tumor volume and performed flow cytometry to analyze immune profile changes post-pDC depletion.
  • Conducted immunohistochemical staining on human HNSCC tissue microarrays to assess pDC infiltration and correlated it with survival and immune markers (Foxp-3, PD-1, TIM-3, LAG-3).

Main Results:

  • pDC depletion significantly delayed tumor growth in the HNSCC mouse model.
  • Depletion of pDCs led to T cell revitalization and decreased proportions of regulatory T cells (Tregs) and monocytic myeloid-derived suppressor cells (MDSCs).
  • Human HNSCC samples showed upregulated pDC infiltration, which was associated with a poor prognosis and correlated with markers like Foxp-3, PD-1, TIM-3, and LAG-3.

Conclusions:

  • Plasmacytoid dendritic cells (pDCs) exert a negative immunomodulatory effect in HNSCC.
  • pDCs represent a potential therapeutic target for enhancing immunotherapy efficacy in HNSCC.

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