A Peripheral Immune Signature of Responsiveness to PD-1 Blockade in Patients With Classical Hodgkin Lymphoma

PD-1 blockade is highly effective in classical Hodgkin lymphoma although the mechanism of action in this largely MHC class I-negative tumor remains undefined. Given this conundrum, we utilized the complementary approaches of T-cell receptor (TCR) sequencing and cytometry by time-of-flight analysis to obtain a peripheral immune signature of responsiveness to PD-1 blockade in clinical trial patients. Increased total and CD4+ TCR repertoire diversity and clonal expansion of singleton T cells were associated with response to anti PD-1 therapy. Additionally, responding patients had an increased abundance of activated NK cells and a newly identified CD3-CD68+CD4+GrB+ subset suggesting a complementary role for innate immunity in the efficacy of PD-1 blockade.