Application of Immune Repertoire Analysis in Differentiating Thyroid Cancer and Large Benign Thyroid Nodules

Abstract This study compares the peripheral T‐cell receptor (TCR) and B‐cell receptor (BCR) immune repertoires among early‐stage papillary thyroid carcinoma (PTC) patients, patients with benign thyroid nodules larger than 4 cm, and healthy controls. Adaptive immune repertoire sequencing is used to analyze peripheral immune profile differences among these groups. Results indicates that early PTC and large benign nodules show significantly higher proportions of expanded clones than healthy controls, reflecting antigen‐driven clonal expansion. By introducing the concept of “publicness,” disease‐specific high‐publicness clonotypes is identified. These clonotypes exhibits distinct V‐J rearrangement characteristics and strong immune heterogeneity. This study further reveals that this immune heterogeneity may be associated with patients' thyroid hormone levels and autoimmune antibody levels. These findings provides new insights into the immunopathological mechanisms of thyroid disorders.