title: Immunological Consequences of JAK Inhibition: Friend or Foe?
abstract: Over the last decade, unparalleled advances have been made within the field of 'Philadelphia chromosome'-negative myeloproliferative neoplasms (MPN) regarding both disease pathogenesis and therapeutic targeting. The discovery of deregulated JAK-STAT signalling in MPN led to the rapid development of JAK inhibitor agents, targeting both mutated and wild-type JAK, which have significantly altered the therapeutic paradigm for patients with MPN. Although the largest population treated with these agents incorporates those with myelofibrosis, increasing data supports potential usage in other MPNs such as essential thromocythaemia and polycythaemia vera. Many MPNs are associated with a hyperinflammatory state and deregulation of immune homeostasis. Over the last few years, research has focused on attempting to decipher the complex and context-dependent changes that contribute to this immune deregulation. Moreover, very recent studies have demonstrated significant JAK inhibitor-mediated effects within the T cell, natural killer cell and dendritic cell compartments following exposure to JAK inhibitors. In parallel, case reports of infections occurring following exposure to ruxolitinib, many of which are atypical, have focused research efforts on delineating JAK inhibitor-associated immunological consequences. Within this review article, we will describe what is currently known about MPN-associated immune deregulation and JAK inhibitor-mediated immunomodulation.
authors: Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 7EH, UK. donal.mclornan@nhs.net.|Department of Haematological Medicine, King's College Hospital NHS Foundation Trust, London, SE5 9NU, UK. donal.mclornan@nhs.net.
authors: Donal P
authors: DP
authors: McLornan
authors: Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 7EH, UK.
authors: Alesia A
authors: AA
authors: Khan
authors: Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London, SE1 7EH, UK.
authors: Claire N
authors: CN
authors: Harrison
mesh_terms: D003713:Dendritic Cells / Q000737:chemistry*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015398:Signal Transduction
chemical_list: D047428:Protein Kinase Inhibitors; D053614:Janus Kinase 2
keywords: Dendritic cells; Immune; JAK; Myeloproliferative; T cells