Untwining Anti-Tumor and Immunosuppressive Effects of JAK Inhibitors-A Strategy for Hematological Malignancies?

The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway propagates signals from a variety of cytokines, contributing to cellular responses in health and disease. Gain of function mutations in JAKs or STATs are associated with malignancies, with being the main driver muta...

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Bibliographic Details
Published in:Cancers 2021-05, Vol.13 (11), p.2611
Main Authors: Klein, Klara, Stoiber, Dagmar, Sexl, Veronika, Witalisz-Siepracka, Agnieszka
Format: Article
Language:English
Subjects:
Autoimmune diseases
Cancer
Clinical trials
Cytokines
Gene expression
Hematology
Homeostasis
Immune response
Immune system
Infections
Janus kinase
Kinases
Leukemia
Lymphocytes
Lymphoma
Malignancy
Mutation
Patients
Phosphorylation
Review
Surveillance
Transcription
Tumors
Viral infections
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Summary:The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway propagates signals from a variety of cytokines, contributing to cellular responses in health and disease. Gain of function mutations in JAKs or STATs are associated with malignancies, with being the main driver mutation in myeloproliferative neoplasms (MPN). Therefore, inhibition of this pathway is an attractive therapeutic strategy for different types of cancer. Numerous JAK inhibitors (JAKinibs) have entered clinical trials, including the JAK1/2 inhibitor Ruxolitinib approved for the treatment of MPN. Importantly, loss of function mutations in JAK-STAT members are a cause of immune suppression or deficiencies. MPN patients undergoing Ruxolitinib treatment are more susceptible to infections and secondary malignancies. This highlights the suppressive effects of JAKinibs on immune responses, which renders them successful in the treatment of autoimmune diseases but potentially detrimental for cancer patients. Here, we review the current knowledge on the effects of JAKinibs on immune cells in the context of hematological malignancies. Furthermore, we discuss the potential use of JAKinibs for the treatment of diseases in which lymphocytes are the source of malignancies. In summary, this review underlines the necessity of a robust immune profiling to provide the best benefit for JAKinib-treated patients.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13112611