Sintilimab promotes the clonal expansion of T cells featuring a shared CDR3 motif in patients with relapsed or refractory classical Hodgkin Lymphoma (r/r cHL)

While PD-1/PD-L1 immunotherapy demonstrates notable efficacy in various tumors, a significant proportion of patients do not experience lasting benefits and may instead suffer from immune-related adverse events (irAEs). This study investigates the dynamics of T cell repertoires in relation to clinical response and irAEs following anti-PD-1 treatment.Although baseline TCRβ-CDR3 analysis did not reveal a clear correlation with clinical outcomes, the expansion of several dominant TCRs in the four patients with three or more blood samples closely aligned with clinical response. The onset of irAE symptoms coincided with significant changes in their dominant TCR clones. Sequence analysis indicated that over half of the dominant TCRβ-CDR3 sequences from these four individuals were shared by all, and four of the nine dominant TCRβ-CDR3 sequences in three responders contained a common signature, which was absent in the non-responder.Our findings suggest that shared TCRβ-CDR3s may recognize similar neoantigens associated with cHL. Some of these common clones demonstrate heightened reactivity and prevalence in specific repertoires. Their expansion could contribute to improved anti-tumor responses following immunotherapy. Dominant TCR analysis may hold clinical value in monitoring and predicting responses and irAEs during checkpoint immunotherapy. <br> <br> <br> <br>