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The ability to identify and track T-cell receptor (TCR) sequences from patient samples is becoming central to the field of cancer research and immunotherapy. Tracking genetically engineered T cells expressing TCRs that target specific tumor antigens is important to determine the persistence of these cells and quantify tumor responses. The available high-throughput method to profile TCR repertoires is generally referred to as TCR sequencing (TCR-Seq). However, the available TCR-Seq data are limited compared with RNA sequencing (RNA-Seq). In this paper, we have benchmarked the ability of RNA-Seq-based methods to profile TCR repertoires by examining 19 bulk RNA-Seq samples across 4 cancer cohorts including both T-cell-rich and T-cell-poor tissue types. We have performed a comprehensive evaluation of the existing RNA-Seq-based repertoire profiling methods using targeted TCR-Seq as the gold standard. We also highlighted scenarios under which the RNA-Seq approach is suitable and can provide comparable accuracy to the TCR-Seq approach. Our results show that RNA-Seq-based methods are able to effectively capture the clonotypes and estimate the diversity of TCR repertoires, as well as provide relative frequencies of clonotypes in T-cell-rich tissues and low-diversity repertoires. However, RNA-Seq-based TCR profiling methods have limited power in T-cell-poor tissues, especially in highly diverse repertoires of T-cell-poor tissues. The results of our benchmarking provide an additional appealing argument to incorporate RNA-Seq into the immune repertoire screening of cancer patients as it offers broader knowledge into the transcriptomic changes that exceed the limited information provided by TCR-Seq.
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This content will become publicly available on September 18, 2026
Making immunology inclusive: a low-cost, high-impact activity for exploring T cell receptor diversity
The function of the immune system is to protect and keep us safe. The immune system surveillance will protect us from foreign antigens entering our body and rogue cells that are no longer under cell cycle control. Considering the most recent pandemic, our students must understand how our immune system works and the function of essential cells involved in this system. However, due to curriculum constraints, particularly at the community college, it may not be feasible for non-biology majors or biology majors to experience the fascinating inner workings of the immune system. Undergraduate students enrolled in an introductory biology, immunology, or microbiology course may not fully grasp the magnitude of receptor diversity embedded in our T cells. The creation of an in-class activity highlights the T cell receptor and provides a deeper understanding of T cell receptor (TCR) diversity. Instructors can use the activity in a lecture or laboratory setting where students work in small groups and use clay to construct different TCRs. Students explore TCR diversity using an interactive V(D)J table of antigen codes. The activity sought to engage students in the classroom to reinforce how T cell diversity contributes to the receptor recognizing the many antigens our bodies encounter daily. The ASPECT (Assessing Student Perspective of Engagement in Class Tool) survey was used to determine students' level of collaboration within their group and their experience with the activity. Results show that students welcomed the activity and felt their contributions and actions during the activity promoted learning.
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- Award ID(s):
- 2316260
- PAR ID:
- 10639581
- Editor(s):
- Vanniasinkam, Thiru
- Publisher / Repository:
- Frontiers
- Date Published:
- Journal Name:
- Frontiers in Education
- Volume:
- 10
- ISSN:
- 2504-284X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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