Tumor-intrinsic resistance mechanisms include (i) neoantigen depletion and defective antigen presentation; (ii) a low tumor mutational burden (TMB), rendering tumors less recognizable to the immune system, (iii) while a high TMB causes chronic antigen exposure, leading to T cell exhaustion; (iv) genetic alterations in tumor cells, e.g., mutations in JAK or IFNG receptors, disrupting IFN signaling and allowing tumors to evade detection and destruction. The gene discussed is IFNA1; the disease is neoplasm.