2. Academic Validation
  3. pDC depletion induced by CD317 blockade drives the antitumor immune response in head and neck squamous cell carcinoma

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

  • Oral Oncol. 2019 Sep:96:131-139. doi: 10.1016/j.oraloncology.2019.07.019.
Lei-Lei Yang 1,  Liang Mao 1,  Hao Wu 1,  Lei Chen 1,  Wei-Wei Deng 1,  Yao Xiao 1,  Hao Li 1,  Lu Zhang 2,  Zhi-Jun Sun 3
Affiliations

Affiliations

  • 1 The 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.
  • 2 Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: luzhang2012@whu.edu.cn.
  • 3 The 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; Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address: sunzj@whu.edu.cn.
PMID: 31422204 DOI: 10.1016/j.oraloncology.2019.07.019
Abstract

Objectives: Dysregulation of immune cells in the tumor microenvironment is a hallmark of head and neck squamous cell carcinoma (HNSCC). Increased infiltration of pDCs has been reported in the microenvironment of HNSCC. However, the precise immunological role of pDC and the therapeutic effects of pDC depletion in HNSCC need to be further investigated.

Materials and methods: CD317 antibodies were applied for depleting pDCs in an immunocompetent transgenic HNSCC mouse model. Tumor volume was monitored. Flow cytometric analysis was conducted for studying the immune profile changes after pDC depletion. In addition, immunohistochemical staining was carried out in a human HNSCC tissue microarray for detecting the infiltration of pDCs. We also analyzed the survival implication of pDCs and its correlation with Other immune related markers in human HNSCC.

Results: pDC depletion in the transgenic HNSCC mouse model significantly delayed tumor growth. After pDCs were depleted, T cells were markedly revitalized, and the proportions of regulatory T cells (Tregs) and monocytic myeloid-derived suppressor cells (MDSCs) were decreased. In human HNSCC microenvironment, pDC infiltration was upregulated and its high infiltration conferred a poor prognosis. Moreover, pDC infiltration was closely correlated with the expression of Foxp-3, PD-1, TIM-3, and LAG-3.

Conclusion: Our findings demonstrated that pDCs play a negative immunomodulatory role in HNSCC and may present as a target for effective immunotherapy.

Keywords

Head and neck cancer; Immune checkpoints; Immunosuppressive cells; Plasmacytoid dendritic cells; Tissue microarray; Transgenic mouse model.

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