The mechanisms of acquired resistance to ICB include, but are not limited to: (1) loss of tumor-suppressor gene, such as PTEN [51, 53] or overexpression of β-catenin [52], (2) up-regulation of inhibitory molecules such as PD-L1 and VISTA [50], (3) loss of neoantigens in the evolved tumors [49], (4) epigenetic silencing of chemokines that facilitate tumor-specific T cell recruitment to tumors [53], (5) loss of B2M required for cell surface expression of HLA-I [54, 55], and (6) loss-of-function mutations in JAK1 or JAK2 [54]. Here, JAK2 is linked to neoplasm.