In summary, our study (i) identifies UBA1 as a biomarker predictive of clinical outcomes in ICB cohorts; (ii) implicates UBA1 in mediating immune evasion, thus promoting tumor progression; (iii) defines JAK1 stabilization as a primary mechanism through which UBA1 inhibition influences immune responses; and (iv) nominates the UBA1–STUB1 axis as an immuno-oncology therapeutic target. Here, UBA1 is linked to neoplasm.