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Updated: Jul 12, 2025

Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
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Infusion Product TNFα, Th2, and STAT3 Activities Are Associated with Clinical Responses to Transgenic T-cell Receptor

Theodore S Nowicki1,2,3,4,5, Cole W Peters1, Crystal Quiros1

  • 1Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of California Los Angeles, Los Angeles, California.

Cancer Immunology Research
|October 23, 2023
PubMed

Insights

Cytokine profiles in T-cell receptor (TCR) T cell therapy products predict treatment success for solid tumors. Specific CD8+ T cell functions and certain cytokines correlate with better responses, aiding biomarker development.

Area of Science:

  • Immunology
  • Oncology
  • Cell Therapy

Background:

  • Transgenic T-cell receptor (TCR) T cell therapies show initial promise for solid tumors but often face treatment failure and relapse.
  • The relationship between cytokine profiles in T-cell therapy products and clinical outcomes remains underexplored.

Purpose of the Study:

  • To investigate the association between preinfusion cytokine profiles of TCR T cell products and clinical response in solid tumor patients.
  • To identify potential biomarkers and therapeutic targets for enhancing TCR T cell therapy efficacy.

Main Methods:

  • Single-cell antigen-dependent secretomic and proteomic analysis of preinfusion TCR T cell therapy products.
  • Correlation analysis of cytokine expression and signaling pathways with clinical response data.

Main Results:

  • Tumor Necrosis Factor alpha (TNFα) functionality in CD8+ T cells and phospho-STAT3 signaling were linked to superior clinical responsiveness.
  • CD4+ T-helper 2 cell cytokine profiles were associated with inferior clinical responses.
  • Preinfusion levels of Interleukin-15 (IL15), Fms-related tyrosine kinase 3 ligand (Flt3-L), and CX3C chemokine ligand 1 (CX3CL1) correlated with therapy response.

Conclusions:

  • Preinfusion cytokine and cellular signaling profiles can predict clinical response to TCR T cell therapy for solid tumors.
  • These findings support the development of predictive biomarkers and targeted strategies for improving TCR T cell therapy outcomes.

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