Table 2 Examples of insights derived from TCR-seq in clinical populations

Hematological malignancy

TCR repertoire diversity significantly higher in patients who received HSCT using DUCB as stem cell sources, as compared with conventional and TCD-derived stem cells

[34]

Post-HSCT GI GVHD

Highly expanded indicator clones identified in GI biopsy at time of diagnosis significantly expand over time as measured in PBMC samples. Furthermore, the degree of expansion is much greater in steroid refractory patients, raising the potential that this could be used to stratify patients for treatment protocols

[36]

Post-HSCT pediatric neuroblastoma

Early infusion of expanded T-cell product in post-HSCT pediatric neuroblastoma patients results in significantly improved TCR repertoire diversity recovery as opposed to late administration

[75]

Ankylosing spondylitis

Many highly expanded autologous clones survive HSCT pre-conditioning regimen and HSCT therapy itself in a patient with ankylosing spondylitis. This suggests that the therapeutic effects of HSCT in this disease are due to an immune system 'reset' resulting from attrition of the T-cell compartment, rather than complete ablation

[38]

Rheumatoid arthritis

1. TCR repertoire in synovium of patients with newly diagnosed RA is dominated by small number of highly expanded T-cell clones, much more so than in patients with established RA

[40]

2. Significant overlap in TCR profile within affected joints in the same patient, with most expanded clone common to most joints

3. No overlap in TCR profile between synovium and PBMC within patient or between patients

TALL

1. TCR-seq can identify minimal residual disease in TALL at higher sensitivities than flow cytometry, the current gold standard

[41]

2. It is possible that the CDR3 sequence may be adapted as a biomarker for risk stratification of minimal residual disease.