In summary, HNSCC patients with higher expression of IGKC, IGHV3-15, IGLV1-40, IGLV1-51, IGLC3, IGLC2, and CD79A may present with a more favorable prognosis, which are available to forecast prognosis and choose patients suitable for mRNA vaccines. Here, IGLC3 is linked to head and neck squamous cell carcinoma.