Dynamics of γδ TCR repertoire during the de-differentiation and treatment course of thyroid cancer [human scRNA]. Dynamics of γδ TCR repertoire during the de-differentiation and treatment course of thyroid cancer [human scRNA]

Although the de-differentiation process of thyroid cancer has been studied, it remains unclear how T cell antigen receptor (TCR) dynamically changes during the cancer progression and treatment. Here we characterized the γδ TCR repertoire along the de-differentiation of thyroid cancers cross-sectionally and investigated the longitudinal changes of TCR components over time in thyroid cancer patients receiving different treatment. We found that better differentiated status was significantly related to greater diversity and lower clonality. Expanded TCRs show enhanced convergent recombination and improved antigen-driven anti-tumor immune responses. The longitudinal study suggested that post-radiotherapeutic immunotherapy led to favorable clinical outcome, which was attributed to the appearance and expansion of neo clonotypes and was validated by scRNA-seq data and murine model experiment. These findings provided a novel understanding in the progression of thyroid cancer and highlighted the role of γδ T cells in anti-tumor immunity. Overall design: We dissociated the pre- and post-treatment tumor tissue on ATC patient and applied single-cell RNA-sequencing (scRNA-seq). ***Raw data for human samples have been submitted to China's Genome Sequence Archive (GSA, https://ngdc.cncb.ac.cn/gsa/) with BioProject Accession: PRJCA014738***