Abstract B011: Mast cells mediate tumor-suppressive effects in head and neck cancer through immune-microenvironmental regulation

Background: Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer with high intratumoral heterogeneity and therapy resistance. Mast cells (MCs), innate immune cells within the tumor microenvironment (TME), exhibit context-dependent roles in tumor progression. Although low MC density has been linked to poor prognosis in head and neck cancers, their functional role in HNSCC remains unclear. Materials and Methods: HNSCC cells were treated with mast cell-conditioned medium (MCCM) derived from both resting and PMA/A23187-activated mast cells. Cellular responses were evaluated by proliferation, colony formation, and cell cycle assays. Key regulatory proteins were analyzed by western blotting. MCCM components were profiled using cytokine/chemokine arrays, and gene expression was validated through single-cell transcriptomic data from patient samples. In vivo anti-tumor effects were assessed via intravenous MCCM administration in HNSCC-bearing mice. Results: MCCM treatment significantly suppressed HNSCC cell proliferation and colony formation, and induced G0/G1 cell cycle arrest, accompanied by upregulation of p21 and downregulation of cyclin D1. Conditioned medium from activated mast cells further enhanced these inhibitory effects. Cytokine and chemokine array analysis identified IGFBP2 as a prominent factor secreted in MCCM. MCCM also reduced phosphorylation of the insulin-like growth factor-1 receptor (IGF1R), suggesting that IGFBP2 may inhibit IGF1R signaling by competing with IGF1 binding. Single-cell transcriptomic analysis of clinical samples revealed that IGFBP2 was predominantly expressed in mast cells and was markedly higher in normal tissues compared to tumor tissues. In vivo, intravenous administration of MCCM significantly inhibited tumor growth in HNSCC-bearing mice relative to controls, supporting the anti-tumor potential of mast cell-derived factors. Conclusion: These findings suggest that mast cells contribute to tumor suppression in HNSCC through the secretion of IGFBP2 and modulation of IGF1R signaling, highlighting their potential as immune-regulatory components in the tumor microenvironment. Citation Format: Ching-Chuan Kuo, Luo-Cih Syu, Chih-Hsiang Huang, Shih-Sheng Jiang, Shau-Ku Huang, Yu-Ting Chou, Jang-Yang Chang, Ko-Jiunn Liu. Mast cells mediate tumor-suppressive effects in head and neck cancer through immune-microenvironmental regulation [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity; 2025 Sep 24-27; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(9 Suppl):Abstract nr B011.