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Updated: Feb 12, 2026

Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
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Increased Tumor Glycolysis Characterizes Immune Resistance to Adoptive T Cell Therapy

Tina Cascone1, Jodi A McKenzie2, Rina M Mbofung2

  • 1Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Cell Metabolism
|April 10, 2018
PubMed

Insights

Tumor glycolysis hinders effective adoptive T-cell therapy (ACT) in cancer. Inhibiting this metabolic pathway can enhance T-cell-mediated antitumor immunity, offering a new therapeutic target.

Area of Science:

  • Immunology
  • Cancer Biology
  • Metabolic Pathways

Background:

  • Adoptive T-cell therapy (ACT) shows promise but faces resistance in most tumors.
  • Molecular mechanisms of ACT resistance are not fully understood.
  • Identifying resistance pathways is crucial for improving cancer immunotherapy.

Purpose of the Study:

  • To investigate the role of tumor glycolysis in resistance to ACT.
  • To explore glycolysis as a potential therapeutic target for enhancing ACT efficacy.

Main Methods:

  • Analysis of glycolysis-related gene expression in patient tumor samples (melanoma and lung cancer).
  • In vitro and in vivo experiments assessing the impact of glycolysis modulation on T-cell killing.
  • Immunohistochemical analysis of tumor tissues and molecular characterization of highly glycolytic melanoma cells.

Main Results:

  • Glycolysis-related genes were upregulated in tumors with poor T-cell infiltration and in ACT-refractory melanoma.
  • Inhibition of tumor glycolysis enhanced T-cell-mediated antitumor immunity.
  • Highly glycolytic melanoma cells showed reduced levels of immunostimulatory molecules IRF1 and CXCL10.

Conclusions:

  • Tumor glycolysis is a key mechanism of resistance to ACT in cancer.
  • Targeting tumor glycolysis represents a promising strategy for combinatorial cancer immunotherapy.
Keywords:
adoptive T cell therapycancer immunotherapyglycolysisimmune resistancemelanomanon-small cell lung cancertumor metabolism reprogramming

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