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

Klara Klein1, Dagmar Stoiber2, Veronika Sexl1

  • 1Department of Biomedical Science, Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.

Cancers
|June 2, 2021
PubMed

Insights

Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway inhibitors (JAKinibs) treat cancers but can suppress immunity. Careful immune profiling is crucial for optimizing JAKinib therapy in patients with hematological malignancies.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway regulates cellular responses and is implicated in various malignancies.
  • Gain-of-function mutations in JAK-STAT pathway components, such as JAK2V617F, drive myeloproliferative neoplasms (MPN).
  • JAK inhibitors (JAKinibs) are therapeutic agents targeting this pathway, with Ruxolitinib approved for MPN treatment.

Purpose of the Study:

  • To review the effects of JAKinibs on immune cells within the context of hematological malignancies.
  • To discuss the therapeutic potential of JAKinibs for lymphocyte-derived malignancies.
  • To emphasize the importance of immune profiling for optimizing JAKinib treatment.

Main Methods:

  • Literature review of current knowledge on JAK-STAT pathway inhibitors and their immunomodulatory effects.
  • Analysis of clinical data regarding JAKinib treatment in MPN patients and associated risks.
  • Discussion of the dual role of JAKinibs in cancer therapy and immune suppression.

Main Results:

  • JAKinibs, while effective in treating MPN, can suppress immune responses, increasing susceptibility to infections and secondary malignancies.
  • Loss-of-function mutations in JAK-STAT pathway members lead to immune deficiencies.
  • The immunomodulatory effects of JAKinibs present a challenge for cancer treatment but are beneficial for autoimmune diseases.

Conclusions:

  • JAKinibs have a complex impact on the immune system, necessitating careful consideration in cancer therapy.
  • Robust immune profiling is essential to personalize JAKinib treatment strategies and maximize patient benefit.
  • Further research is needed to balance the oncogenic and immunosuppressive effects of JAKinibs in hematological malignancies.
Keywords:
JAKJAK inhibitorNK cellsSTATT cellsleukemia

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