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Updated: Feb 14, 2026

Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
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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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STAT3-enhancing germline mutations contribute to tumor-extrinsic immune evasion

Daniel Kogan1,2, Alexander Grabner3, Christopher Yanucil4

  • 1Technische Universität München, Munich, Germany.

The Journal of Clinical Investigation
|February 14, 2018
PubMed

Insights

Host germline variants, specifically in FGFR4, can enhance STAT3 signaling, promoting cancer immune evasion. This study reveals how these variants suppress antitumor immune responses, impacting cancer progression and patient prognosis.

Area of Science:

  • Immunology
  • Cancer Biology
  • Genetics

Background:

  • Cancer progression involves immune evasion and suppressed antitumor responses, often linked to tumor factors.
  • The role of host germline variants in dictating cancer immunosuppression remains largely unexplored.
  • A common FGFR4 (CD334) germline mutation (rs351855 G/A) enhances STAT3 signaling, correlating with poor cancer prognosis.

Purpose of the Study:

  • To investigate the impact of host-specific germline variants on cancer immunosuppression.
  • To elucidate the role of FGFR4 variants and STAT3 signaling in immune evasion mechanisms.
  • To determine if germline variants can impede anti-tumor immune cell infiltration.

Main Methods:

  • Utilized rs351855 SNP-knockin and Fgfr4-knockout transgenic mouse models.
  • Assessed genotype-specific immunological functions in vivo.
  • Employed knockin mouse models for lung and breast cancers to study tumor-extrinsic effects.

Main Results:

  • Demonstrated genotype-specific suppression of the CD8/CD4+FOXP3+CD25+ regulatory T cell ratio.
  • Established that STAT3-enhancing germline variants impede CD8 T cell tumor infiltration in lung and breast cancer models.
  • Identified tumor-extrinsic functions of germline variants in modulating the immune microenvironment.

Conclusions:

  • Host-specific germline variants, particularly in FGFR4, can promote cancer immune evasion.
  • STAT3-enhancing germline variants contribute to immunosuppression through pleiotropic effects on immune cells.
  • These findings highlight germline genetics as a critical factor in cancer progression and immune response.
Keywords:
Complex traitsGenetic variationGeneticsHomeostasisOncology

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