The Antitumor Mechanism of Immuno-flap Treatment in a Rat Model of Head and Neck Cancer

Abstract Background Local recurrence after surgical resection is a major clinical challenge in patients with advanced head and neck cancer (HNC). We previously reported using transfer of a flap treated with dendritic cells (DCs) (“immuno-flap”) as a novel cancer immunotherapy in a rat model of HNC. However, several problems, such as the improvement of DC yield and the verification of DC tracking, remained to be solved. Methods The initial DC production protocol was revisited, and the specific mechanism of the antitumor effect associated with functional DCs was investigated. Results The yield and the purity of potent DCs were improved, and an in vivo tracking experiment revealed that, when injected into the skin flap, the DCs migrated to local lymph nodes within 24 h. In an in vivo long-term protection model in which DCs were injected into the skin flap weekly for 4 weeks, no strong antitumor effect on HNC tumor progression was observed, but a remarkable pathological effect was verified. Moreover, an enzyme-linked immunospot assay demonstrated that more CD8⁺ T cells positive for PD-1, CD40LIG, and TNF-α expression and producing interferon γ specific to SCC-158 tumor cells were identified in tumors and spleens from rats treated using immuno-flaps. Conclusions These results indicate that immuno-flap transfer to prevent local recurrence in patients with HNC has potential for clinical application given the improved yield and quality of antitumor DCs.