Invariant Natural Killer T Cell-Based Immunotherapy Using α-Galactosylceramide-Pulsed CD14⁺ Monocytes for Advanced...

Gallbladder cancer is a rare and aggressive malignancy. Patients with unresectable or metastatic disease generally have poor outcomes despite standard chemotherapy. Novel immunotherapeutic strategies that enhance antitumor immunity are of considerable clinical interest. Invariant natural killer T (iNKT) cells rapidly produce cytokines and activate immune effector cells, representing a potential target for immunotherapy.

We report a case of advanced gallbladder cancer treated with gemcitabine chemotherapy in combination with autologous iNKT cell-targeted therapy. Peripheral blood CD14⁺ monocytes were isolated, pulsed in vitro with α-galactosylceramide (α-GalCer), and administered intravenously to activate iNKT cells in vivo. Post-treatment contrast-enhanced computed tomography scan demonstrated shrinkage of multiple liver metastases and reduction in intra-abdominal lymphadenopathy. Liver function markers improved, and interferon-γ-producing cells increased, indicating systemic immune activation. The therapy was well tolerated, with only mild transient fever observed.

Although the specific contribution of immunotherapy cannot be definitively separated from concomitant chemotherapy, the temporal association between α-GalCer-pulsed CD14⁺ monocytes (GC-MO) administration, immune activation, and clinical improvement suggests a potential synergistic effect. Activation of iNKT cells may enhance antitumor immunity, contributing to tumour regression and improved hepatic function. This case highlights the feasibility and safety of combining iNKT-targeted therapy with standard chemotherapy in advanced gallbladder cancer.

iNKT cell-targeted immunotherapy using GC-MO may serve as a promising adjunctive strategy for advanced gallbladder cancer. Further studies are warranted to validate its efficacy and define its role in combination with conventional chemotherapy.

Invariant natural killer T (iNKT) cells play an important role in antitumor immunity by rapidly producing cytokines and activating multiple immune effector cells, including NK cells and cytotoxic T lymphocytes.α-Galactosylceramide-pulsed CD14⁺ monocytes can activate iNKT cells and induce systemic immune responses.Combination therapy with chemotherapy and iNKT cell-targeted immunotherapy may contribute to tumour regression and immune activation in patients with advanced gallbladder cancer.