Monitoring the effect of immunomodulatory treatment on the immune repertoire using the IGX platform

Repertoire analysis is rapidly gaining traction as a tool for monitoring patients receiving immunotherapy treatment. Repertoire analysis combines the unique sequence of T and B cell receptors and high throughput sequencing to identify specific T and B cell clones in vivo. However, the management, analysis, interpretation, and implementation of repertoire data in research and clinical workflows is challenging and requires specialist methodology and software. The ImmunoGenomiX (‘IGX’) platform is a new versatile platform for the management, analysis, and interpretation of high-throughput repertoire sequencing data. In this study, we present the application of repertoire fingerprinting using the IGX platform to monitor the effect of lenalidomide treatment in patients with del(5q) myelodysplastic syndromes [1]. First, to verify that the IGX platform performs state-of-the-art analysis, we performed benchmark studies for both TCR as well as BCR data, showing that the IGX platform produces accurate and reliable immune repertoire profiles. Then, we monitored the T and B cell repertoire of del(5q) myelodysplastic syndrome patients during lenalidomide treatment. Patient as well as healthy donor IGH and TRB chains were Illumina sequenced. After obtaining the repertoire profiles, we applied TCR specificity clustering to group TCRs that have a similar specificity, and we calculated receptor generation probabilities to identify those TCR clusters that have likely undergone antigen-specific expansion. We show that lenalidomide treatment induced proliferation of shared T cell response patterns across patients, which are indicative of myelodysplastic syndromes-specific T cell responses. These findings suggest that lenalidomide not only alters the functional T cell state, but also impacts the T and B cell repertoire composition in del(5q) myelodysplastic syndromes.