Targeting CNS Lymphoma with Intravenous Axicabtagene Ciloleucel: Evidence for Transcriptional Evolution Towards a Prominent Interferon Signature in CAR-T Cells Trafficking to the Tumor Site

In an effort to better understand the key mechanisms of action and resistance in primary and secondary central nervous system lymphomas and regarding CAR T-cell therapies, researchers conducted a pilot trial of axicabtagene ciloleucel in patients with relapsed and/or refractory disease. Using both 5’ 10x single-cell RNA sequencing and T-cell receptor sequencing, a major distinction between blood and cerebrospinal fluid CAR T cells was found at the level of individual CAR T-cell clones, suggesting interferon pathway enrichment may play a role in CAR T-cell therapeutic efficacy in these disease.