Background: Although significant progress has been made in immune checkpoint inhibitor (ICI) treatment of advanced squamous cell carcinoma (SqCC), most patients still experience acquired drug resistance. Methods: We used a dendritic cell-based neoantigen vaccine combined with ICIs to treat advanced SqCC in a PD-1 blockade-resistant patient. Results: The follow-up of this patient after 12 months revealed significant tumor regression. We also identified a new JAK1 ICI-resistant mutation that could become a potential universal neoantigen target for tumor vaccines. Conclusion: Individualized management of advanced SqCC through a combined neoantigen vaccine and ICI administration could yield beneficial clinical outcomes. Vaccines targeting anti-PD-1-resistant JAK1 mutations might be of particular benefit to a specific group of solid tumor patients.
Keywords: JAK1; PD-1; advanced squamous cell carcinoma; neoantigen vaccine; personalized therapy.
Immunotherapy based on immune checkpoint inhibitors (ICIs) is very effective in lung cancer treatment. However, many patients with initial response will later develop resistance. There are not many treatment options for patients with drug resistance. Herein, we report a patient with lung cancer who became resistant to ICI, treated with personalized vaccine plus ICI. Based on the patient's own somatic mutational profile, personalized neoantigen vaccines were designed and manufactured unique to the patient. Our report indicated that personalized vaccine plus ICI was safe and might overcome ICI resistance. A new ICI resistance mutation on JAK1 as a potential universal neoantigen target for off-the-shelf vaccine was found, which is promising for the effective treatment of a specific group of patients with JAK1 mutations.