CAR+ and CAR- T cells share a differentiation trajectory into an NK-like subset after CD19 CAR T cell infusion in patients with B cell malignancies.

Chimeric antigen receptor (CAR) T cell therapy is effective in treating B cell malignancies, but factors influencing the persistence of functional CAR+ T cells, such as product composition, patients' lymphodepletion, and immune reconstitution, are not well understood. To shed light on this issue, here we conduct a single-cell multi-omics analysis of transcriptional, clonal, and phenotypic profiles from pre- to 1-month post-infusion of CAR+ and CAR- T cells from patients from a CARTELL study (ACTRN12617001579381) who received a donor-derived 4-1BB CAR product targeting CD19. Following infusion, CAR+ T cells and CAR- T cells shows similar differentiation profiles with clonally expanded populations across heterogeneous phenotypes, demonstrating clonal lineages and phenotypic plasticity. We validate these findings in 31 patients with large B cell lymphoma treated with CD19 CAR T therapy. For these patients, we identify using longitudinal mass-cytometry data an association between NK-like subsets and clinical outcomes at 6 months with both CAR+ and CAR- T cells. These results suggest that non-CAR-derived signals can provide information about patients' immune recovery and be used as correlate of clinically relevant parameters.

TMS-EEG approach unveils brain mechanisms underlying conscious and unconscious face perception.

BACKGROUND: Conscious perception of external stimuli has been related to recurrent activity in distributed cortical networks, although brain mechanisms controlling unconscious processing and stimuli access to conscious report need to be clarified. OBJECTIVE: This study aims at investigating modulations in cortical excitability related to conscious perception and unconscious processing of face stimuli with different visibility levels. METHODS: We used TMS-EEG over the right occipital face area (rOFA), or the right premotor cortex (rPMC) as control site, to measure cortical excitability during a backward masking paradigm with individually defined stimuli visibility. RESULTS: Event related potentials showed significant differences for faces compared to houses, and detected faces compared to missed ones, 200 ms post target onset. TMS over rOFA, but not over rPMC, triggered a relative positivity starting 150 ms post target when faces with high visibility were consciously reported. Moreover, rOFA TMS evoked differential responses for high versus low visible faces in conscious and unconscious processing at 290-390 and 180-240 ms, respectively. CONCLUSION: Results unveiled a causal link between rOFA excitability and late responses related to access to conscious perception, suggesting a critical role of recurrent activity, but distinct components, for consciously perceived stimuli and unconscious face processing.