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Cholangiocarcinomas are rare but aggressive liver tumors of high lethality with scarce treatment options. Here we report on the follow-up of a patient diagnosed with an intrahepatic cholangiocarcinoma who experienced repeated tumor recurrences including distant metastasis, therefore facing a dismal prognosis. At present, this patient is tumor-free for more than 8 years following repeated surgery and application of two successive personalized vaccines. In-depth functional immune cell analyses revealed a dominant CD4+ T-cell response against the vaccine antigens with infiltration of the tumor site and immune responses prevailing for years following the last vaccine administration. Additionally, spontaneous tumor neoantigen-specific CD4+ and CD8+ T-cell responses have been detected, which might have contributed to the outstanding outcome witnessed in this patient. This case report highlights vaccination strategies targeting non-mutated antigens as well as the increasingly recognized central role of antitumor CD4+ T cells.