Related Experiment Video

Updated: Jan 22, 2026

Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
08:32

Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors

Published on: June 7, 2018

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Sensitization to immune checkpoint blockade through activation of a STAT1/NK axis in the tumor microenvironment

Rachael M Zemek1,2, Emma De Jong3, Wee Loong Chin2,4,5

  • 1School of Biomedical Sciences, University of Western Australia, M503, Crawley, WA 6009, Australia.

Science Translational Medicine
|July 19, 2019
PubMed

Insights

Identifying the tumor microenvironment is key for effective cancer immunotherapy. Responsive tumors show specific inflammatory signals and natural killer (NK) cells, which can be therapeutically enhanced to improve treatment outcomes.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Cancer immunotherapy, particularly immune checkpoint blockade (ICB), shows promise but benefits only a subset of patients.
  • Understanding the biological factors determining ICB response is crucial for developing effective combination treatments.
  • Inbred mouse models with dichotomous responses to ICB offer a platform to study pretreatment tumor microenvironments.

Purpose of the Study:

  • To define the pretreatment tumor microenvironment associated with effective responses to cancer immunotherapy.
  • To identify biomarkers predictive of response to immune checkpoint blockade (ICB).
  • To explore therapeutic strategies to sensitize nonresponsive tumors to ICB.

Main Methods:

  • Comparative analysis of cellular composition and gene expression profiles in responsive versus nonresponsive tumors from mice before ICB.
  • Validation of findings in human cancer patient cohorts treated with ICB antibodies.
  • Experimental manipulation of the tumor microenvironment using interferon-γ (IFNγ), poly(I:C), and anti-interleukin-10 (IL-10) antibody in mice.

Main Results:

  • Responsive tumors exhibit an inflammatory gene signature with up-regulated signal transducer and activator of transcription 1 (STAT1) and Toll-like receptor 3 (TLR3) signaling, and down-regulated interleukin-10 (IL-10) signaling.
  • Increased infiltration of activated natural killer (NK) cells is essential for ICB response.
  • Pretreatment with IFNγ, poly(I:C), and anti-IL-10 antibody enhanced ICB efficacy by promoting NK cell infiltration and increasing cure rates.

Conclusions:

  • A specific pretreatment tumor microenvironment, characterized by inflammatory signatures and NK cell infiltration, predicts response to ICB.
  • Therapeutic strategies targeting this microenvironment can sensitize tumors to ICB, leading to improved outcomes.
  • Biomarker-driven patient management can identify individuals who would benefit from sensitizing therapies prior to ICB.

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