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Updated: Apr 21, 2026

Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
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Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology

Published on: May 2, 2025

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JAK inhibition in PD-1 immunotherapy and tumor microenvironment

Ziyuan Liu1, Jiaqi Liu2, Hongyu Chu3

  • 1Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin, China.

Frontiers in Immunology
|April 20, 2026
PubMed

Insights

Combining Janus kinase (JAK) inhibitors with PD-1 blockade may overcome cancer therapy resistance. This approach targets chronic inflammation and immunosuppressive tumor microenvironments (TME) to improve patient outcomes.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have transformed cancer treatment.
  • Therapeutic response durability is often limited by chronic inflammation and immunosuppressive tumor microenvironments (TME).
  • The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway integrates cytokine signals that drive resistance to cancer therapies.

Purpose of the Study:

  • To elucidate the role of JAK/STAT signaling in shaping the tumor immune microenvironment (TME) in hematologic and solid tumors.
  • To explore the rationale for repurposing JAK inhibitors as adjuvants to cancer immunotherapy.
  • To review evidence supporting the combination of JAK inhibition and PD-1 blockade for overcoming resistance to immune checkpoint inhibitors.

Main Methods:

  • Comprehensive review of preclinical and clinical evidence.
  • Analysis of molecular crosstalk between JAK/STAT signaling and immune cells within the TME.
  • Examination of the impact of JAK/STAT aberrant activation on malignant progression and immune evasion.

Main Results:

  • Aberrant JAK/STAT activation promotes cancer progression, upregulates PD-L1, and creates an immunosuppressive TME by recruiting myeloid-derived suppressor cells (MDSCs) and polarizing macrophages.
  • JAK/STAT signaling plays a multifaceted role in the immune architecture of tumors.
  • Combining JAK inhibitors with PD-1 blockade shows promise in preclinical and clinical studies.

Conclusions:

  • JAK/STAT signaling is a critical regulator of the tumor immune microenvironment and a key driver of resistance to immunotherapy.
  • Repurposing JAK inhibitors alongside PD-1 blockade offers a promising strategy to disrupt inflammatory feedback loops and reprogram the TME.
  • This synergistic approach holds potential for improving outcomes in patients with refractory malignancies.
Keywords:
JAK/STAT signaling pathwayimmune checkpoint inhibitorsimmunosuppressionimmunotherapy resistancetumor microenvironment

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