Augmenting Chemokine CCL21 Enhances the Effectiveness of CTLA4 Blockade Immunotherapy for Head and Neck Squamous Carcinoma

Abstract Recent studies have demonstrated promising outcomes in the treatment of head and neck squamous cell carcinoma (HNSCC) through immune checkpoint cytotoxic T lymphocyte antigen 4 (CTLA4) blockade. However, although the potential of CTLA4 in HNSCC treatment is evident, its underlying mechanism of action remains unclear, leaving room for optimization. Research has revealed that C–C motif chemokine ligand (CCL21) possesses the ability to activate T-cell responses and enhance the immune response in the tumor microenvironment. CCL21 has demonstrated antitumor properties in various cancer types. Combing CCL21 with immune checkpoints inhibitors can amplify the synergistic antitumor benefits. This study applied a combination of CTLA4 monoclonal antibody and chemokine CCL21 in the immunotherapy of HNSCC. Furthermore, this optimized therapeutic approach notably enhances the impact on the activation of immune T cells in the tumor microenvironment and elucidates its regulatory influence on the key proteins of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. These findings offer an efficacious immunotherapeutic strategy for HNSCC.