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VEGF-A blockade overcomes liver metastases resistance to chemoimmunotherapy in patients with advanced non-squamous

Matthieu Roulleaux-Dugage1,2,3, Andrey Yurchenko4, Sergey Nikolaev4

  • 1Laboratoire d'Immunomonitoring, INSERM U1363, Gustave Roussy, Villejuif, France.

Journal for Immunotherapy of Cancer
|June 23, 2026
PubMed
Abstract

Insights

Adding bevacizumab to chemoimmunotherapy improved survival for non-small cell lung cancer patients with liver metastases. This combination therapy may overcome resistance by targeting the immunosuppressive tumor microenvironment.

Area of Science:

  • Oncology
  • Immunotherapy
  • Translational Research

Background:

  • Liver metastases (LMs) in non-squamous non-small cell lung cancer (ns-NSCLC) limit immune checkpoint blockade efficacy.
  • The tumor microenvironment (TME) in LMs is often immunosuppressive, hindering anti-cancer immune responses.

Purpose of the Study:

  • To evaluate if vascular endothelial growth factor (VEGF)-A blockade with bevacizumab can enhance chemoimmunotherapy in ns-NSCLC patients with LMs.
  • To compare chemoimmunotherapy with and without bevacizumab in this specific patient population.

Main Methods:

  • Analysis of data from phase III IMpower130 and IMpower150 trials in treatment-naïve ns-NSCLC patients.
  • Stratification by liver metastasis status and assessment of survival outcomes using Kaplan-Meier and Cox regression.
  • Characterization of the LM TME using bulk and single-cell RNA sequencing.

Main Results:

  • In IMpower150, adding bevacizumab to chemotherapy plus atezolizumab significantly improved progression-free survival and overall survival in LM+ patients.
  • This survival benefit was not observed in patients without LMs or in the IMpower130 trial without bevacizumab.
  • Exploratory analyses revealed a myeloid-rich, lymphocyte-poor TME in LMs, with evidence of VEGF-A signaling crosstalk.

Conclusions:

  • Bevacizumab combined with chemoimmunotherapy shows promise for improving survival in ns-NSCLC patients with LMs.
  • This benefit may be due to bevacizumab disrupting VEGF-A-driven immunosuppression in the liver TME.
  • Further prospective studies are needed to confirm these findings.
Keywords:
Escape/evasionImmune Checkpoint InhibitorImmunotherapyNon-Small Cell Lung CancerTumor microenvironment - TME

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