Related Experiment Video

Updated: Jul 16, 2026

A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
06:38

A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies

Published on: April 12, 2017

Immunometabolic Stress and Immune Suppression in Clear-Cell Renal Cell Carcinoma: Perspectives in Therapeutic

Tuong-Vi Nguyen1, Tien Hsu1,2

  • 1Department of Biomedical Sciences and Engineering, National Central University, 300 Zhongda Rd., Taoyuan 320317, Taiwan.

International Journal of Molecular Sciences
|July 15, 2026
PubMed

Insights

Hypoxia in clear-cell renal cell carcinoma (ccRCC) drives metabolic changes that impair T-cell function. Targeting these immunometabolic pathways offers new therapeutic strategies for this kidney cancer.

Area of Science:

  • Oncology
  • Immunology
  • Metabolic Research

Background:

  • Solid tumors, including clear-cell renal cell carcinoma (ccRCC), often develop hypoxia during progression.
  • Hypoxia in ccRCC is linked to loss of the von Hippel-Lindau (VHL) gene and activated hypoxia-inducible factor (HIF) signaling, leading to significant metabolic reprogramming.
  • Despite advances, durable responses to therapies like immune checkpoint inhibitors remain limited in ccRCC.

Purpose of the Study:

  • To review the current understanding of hypoxia-driven immunometabolic interactions in ccRCC.
  • To explore how targeting these metabolic pathways could enhance therapeutic strategies for ccRCC.

Main Methods:

  • Literature review and synthesis of existing research on hypoxia, metabolism, and immune dysfunction in ccRCC.
  • Analysis of key metabolic pathways implicated in ccRCC immunometabolism.

Main Results:

  • Hypoxia induces profound metabolic alterations in ccRCC, creating a unique 'immune-hot yet immunosuppressed' tumor microenvironment.
  • Key metabolic pathways involved include lactate acidosis, arginine and tryptophan depletion, kynurenine-mediated T-cell exhaustion, and adenosine-driven immune suppression.
  • These hypoxia-associated metabolic changes contribute to T-cell dysfunction and exhaustion within the ccRCC tumor microenvironment.

Conclusions:

  • ccRCC is characterized by extensive metabolic rewiring driven by hypoxia, impacting the tumor immune landscape.
  • Targeting specific immunometabolic pathways represents a promising avenue for developing novel and more effective therapeutic strategies against ccRCC.
Keywords:
clear-cell renal cell carcinomahypoxiaimmune suppressionimmunometabolismkynurenine pathwaymetabolic reprogramming

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