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Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus
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Pipeline to characterize antigen-specific TCR repertoires in tumors: Examples from an HPV16 tumor model
1Department of Thoracic/Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, United States; Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Abstract:
Immunotherapies that improve T cell-based anti-tumor immunity have revolutionized cancer. However, the underlying mechanisms of cancer immune responsiveness are still not fully understood. Using immune competent mice for preclinical development of novel mono and combination therapies is a common strategy, and to monitor the T cell response inside tumors and in the periphery offers valuable insight. T cells recognize target cells by based on the binding between the T cell receptor (on T cells) and peptides presented on MHC-I (on tumor cells). As such, the T cell receptor can be used as a "barcode" for a specific T cell clone. Via TCR sequencing, the sequence of this "barcode" can be identified, and eventually, the TCR repertoire in a sample can be assessed as a whole. This information can be useful in multiple ways, including but not excluded to: (i) tracing specific clones in tissues and in blood, and (ii) determine clonal expansion of a specific clone in the tumor microenvironment which suggest anti-tumor activity of the clone in question. This protocol can be used as a guide from experimental design through TCR-sequencing to analysis of the repertoire. Instead of being specifically focused on one type of TCR-sequencing, this protocol can be used as a resource and contains links and references to useful information that has to be considered. Lastly, certain common metrics when analyzing the TCR repertoire are given and discussed.
Insights
T cell receptor (TCR) sequencing allows researchers to track specific T cell clones and assess their expansion within tumors. This method provides valuable insights into anti-tumor immunity for cancer immunotherapy research.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Cancer immunotherapies have transformed cancer treatment, but mechanisms of immune response remain unclear.
- Preclinical studies in mice are crucial for developing new cancer therapies.
- Monitoring T cell responses in tumors and circulation offers key insights into treatment efficacy.
Purpose of the Study:
- To provide a comprehensive protocol for T cell receptor (TCR) sequencing in preclinical cancer research.
- To guide experimental design, TCR sequencing, and repertoire analysis.
- To serve as a resource for understanding TCR repertoire metrics and their implications.
Main Methods:
- Utilizing T cell receptor (TCR) sequencing to identify and track specific T cell clones.
- Analyzing the TCR repertoire within tumors and peripheral blood.
- Applying TCR sequencing for tracing T cell clones and assessing clonal expansion.
Main Results:
- TCR sequencing enables the identification of specific T cell clones, acting as a unique molecular barcode.
- Clonal expansion within the tumor microenvironment indicates potential anti-tumor activity.
- The protocol facilitates tracing T cell clones across different tissues and blood samples.
Conclusions:
- TCR sequencing is a powerful tool for dissecting T cell responses in cancer immunotherapy.
- Understanding TCR repertoire dynamics is essential for evaluating the effectiveness of anti-cancer therapies.
- This protocol offers a standardized approach to TCR sequencing and analysis in preclinical models.
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