Evaluating T-cell cross-reactivity between tumors and immune-related adverse events with TCR sequencing: pitfalls in interpretations of functional relevance
| Autor: | Jiajia Zhang, Franco Verde, Tricia Cottrell, Hans Hammers, Kellie N Smith, Janis Taube, Boyang Zhang, Genevieve J Kaunitz, Poromendro Burman, Hok-Yee Chan, Jody E Hooper, Mohamad E Allaf, Hongkai Ji |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Journal for ImmunoTherapy of Cancer, Vol 9, Iss 7 (2021) |
| Druh dokumentu: | article |
| ISSN: | 2051-1426 84144378 |
| DOI: | 10.1136/jitc-2021-002642 |
| Popis: | T-cell receptor sequencing (TCRseq) enables tracking of T-cell clonotypes recognizing the same antigen over time and across biological compartments. TCRseq has been used to test if cross-reactive antitumor T cells are responsible for development of immune-related adverse events (irAEs) following immune checkpoint blockade. Prior studies have interpreted T-cell clones shared among the tumor and irAE as evidence supporting this, but interpretations of these findings are challenging, given the constraints of TCRseq. Here we capitalize on a rare opportunity to understand the impact of potential confounders, such as sample size, tissue compartment, and collection batch/timepoint, on the relative proportion of shared T-cell clones between an irAE and tumor specimens. TCRseq was performed on tumor-involved and -uninvolved tissues, including an irAE, that were obtained throughout disease progression and at the time of rapid autopsy from a patient with renal cell carcinoma treated with programmed death-1 (PD-1) blockade. Our analyses show significant effects of these confounders on our ability to understand T-cell receptor overlap, and we present mitigation strategies and study design recommendations to reduce these errors. Implementation of these strategies will enable more rigorous TCRseq-based studies of immune responses in human tissues, particularly as they relate to antitumor T-cell cross-reactivity in irAEs following checkpoint blockade. |
| Databáze: | Directory of Open Access Journals |
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