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Characterization and Comparison of GITR Expression in Solid Tumors.

Luis Vence1, Samantha L Bucktrout2,3, Irina Fernandez Curbelo1

  • 1The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center, Houston, Texas.

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|July 31, 2019
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Summary
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An anti-GITR antibody showed therapeutic benefits in mouse models, with efficacy linked to T-cell presence. Human tumor analysis identified NSCLC, renal cell carcinoma, and melanoma as key targets for this immunotherapy.

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Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • Glucocorticoid-induced tumor necrosis factor receptor (GITR) is a target for cancer immunotherapy.
  • Understanding GITR expression in the tumor microenvironment is crucial for developing effective therapies.

Purpose of the Study:

  • To evaluate the therapeutic effects of an anti-GITR antibody (21B6) in mouse tumor models.
  • To characterize GITR expression in T-cell subsets across seven human solid tumor types.

Main Methods:

  • Experiments involved injecting tumor cells into mice and treating them with the anti-GITR antibody 21B6.
  • Tumor growth and survival were monitored.
  • GITR expression was analyzed using flow cytometry (FC) and immunohistochemistry (IHC) in both mouse models and human tumor samples.

Main Results:

  • The anti-GITR antibody demonstrated therapeutic benefits, with varying efficacy across different mouse tumor models (CT26 > MC38 > B16).
  • The presence of CD8 T cells and effector CD4 T cells in the tumor infiltrate correlated with treatment response.
  • Non-small cell lung cancer (NSCLC), renal cell carcinoma, and melanoma exhibited the highest GITR expression levels, particularly on CD4+ Foxp3+ regulatory T cells.

Conclusions:

  • The study highlights the differential efficacy of anti-GITR therapy in various tumor contexts.
  • NSCLC, renal cell carcinoma, and melanoma are identified as promising candidates for prioritizing anti-GITR therapy development based on high GITR expression.