Macrophage-derived dendritic cells enhance antitumor immunity in a mouse model of head and neck squamous cell carcinoma

Abstract

Purpose: This study investigates the therapeutic potential of bone marrow macrophages-derived dendritic cells (BMΦDCs) in enhancing antitumor immunity against head and neck squamous cell carcinoma (HNSCC), focusing on their effects in inhibiting tumor growth, reducing metastasis, and modulating the tumor microenvironment.

Methods: BMΦDCs were generated by culturing bone marrow cells with macrophage colony-stimulating factor (M-CSF) followed by granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). MTCQ-1 tumor lysates were used for antigen loading. The phenotypic characteristics of BMΦDCs were analyzed using flow cytometry. In vivo antitumor efficacy was assessed in subcutaneous and lung metastasis models in immunocompetent C57BL/6 mice. Tumor growth was monitored, and tumor tissues were collected for histological analysis using hematoxylin and eosin (H&E), Masson's trichrome, and anti-CD8 staining.

Results: BMΦDCs displayed higher maturation marker expression (CD40, CD86) compared to traditional BMDCs. In the subcutaneous tumor model, BMΦDCs significantly inhibited tumor growth and enhanced cytotoxic T lymphocyte (CTL) activity. In the lung metastasis model, BMΦDCs effectively reduced metastatic burden. Histological analysis revealed increased CD8⁺ T cell infiltration and reduced tumor fibrosis in BMΦDC-treated mice. No significant toxicity or organ damage was observed.

Conclusions: BMΦDCs are a promising immunotherapeutic approach for HNSCC, demonstrating superior antitumor efficacy, enhanced immune responses, and excellent biosafety. These findings highlight the potential of BMΦDCs in advancing cancer immunotherapy.

Keywords: Dendritic cell vaccines; Head and neck squamous cell carcinoma; Tumor immunotherapy.