Figure 2.

Working model of MPN immunopathogenesis and related immunotherapeutic strategies. In the MPN-associated BM niche, relevant immunological dynamics are sustained by the mutant clone, creating positive feedback loops (black arrows), which can directly promote tumor progression (through chronic inflammation, inducing genomic instability and ROS-dependent mutagenesis) as well as support the permissive microenvironment (by loss of MPN-specific protective immunity). Both immunopathogenetic features can be targeted by novel therapeutic approaches, aiming to inhibit JAK2 constitutive signaling, modulate the TME and restore antitumor immunosurveillance. JAKi: JAK inhibitors, TME: tumor microenvironment, ICIs: immune checkpoint inhibitors, ⊥: inhibition, X: block.