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Updated: Sep 26, 2025
Author Spotlight: Optimized Protocol for Detecting Antigen-Specific T Cells in Mouse Lungs Using Tetramers
Published on: July 19, 2024
A phenotypic signature that identifies neoantigen-reactive T cells in fresh human lung cancers
Ken-Ichi Hanada1, Chihao Zhao1, Raul Gil-Hoyos1
1Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
A common theme across multiple successful immunotherapies for cancer is the recognition of tumor-specific mutations (neoantigens) by T cells. The rapid discovery of such antigen responses could lead to improved therapies through the adoptive transfer of T cells engineered to express neoantigen-reactive T cell receptors (TCRs). Here, through CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) and TCR-seq of non-small cell lung cancer (NSCLC) tumor-infiltrating lymphocytes (TILs), we develop a neoantigen-reactive T cell signature based on clonotype frequency and CD39 protein and CXCL13 mRNA expression. Screening of TCRs selected by the signature allows us to identify neoantigen-reactive TCRs with a success rate of 45% for CD8+ and 66% for CD4+ T cells. Because of the small number of samples analyzed (4 patients), generalizability remains to be tested. However, this approach can enable the quick identification of neoantigen-reactive TCRs and expedite the engineering of personalized neoantigen-reactive T cells for therapy.
Insights
Researchers developed a new method to identify T cells that recognize cancer neoantigens. This signature helps find T cell receptors for personalized cancer immunotherapy, improving treatment development for non-small cell lung cancer.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Successful cancer immunotherapies rely on T cells recognizing tumor-specific mutations (neoantigens).
- Rapid identification of neoantigen-reactive T cells is crucial for developing advanced therapies like adoptive T cell transfer.
- Engineering T cells with specific T cell receptors (TCRs) enhances their anti-tumor activity.
Purpose of the Study:
- To develop a signature for identifying neoantigen-reactive T cells from non-small cell lung cancer (NSCLC) tumors.
- To assess the efficacy of this signature in selecting TCRs for therapeutic applications.
- To expedite the engineering of personalized T cells for cancer immunotherapy.
Main Methods:
- Utilized CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) and TCR-seq.
- Analyzed tumor-infiltrating lymphocytes (TILs) from NSCLC patients.
- Developed a neoantigen-reactive T cell signature based on clonotype frequency, CD39 protein, and CXCL13 mRNA expression.
Main Results:
- Identified a signature to screen for neoantigen-reactive TCRs.
- Achieved a 45% success rate for CD8+ T cells and 66% for CD4+ T cells in identifying neoantigen-reactive TCRs.
- Demonstrated the potential for rapid identification of therapeutically relevant TCRs.
Conclusions:
- The developed signature enables efficient identification of neoantigen-reactive TCRs.
- This approach can accelerate the engineering of personalized T cells for cancer therapy.
- Further validation in larger patient cohorts is needed to confirm generalizability.
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