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Intratumoral plasma cells predict outcomes to PD-L1 blockade in non-small cell lung cancer

Inhibitors of the programmed cell death-1 (PD-1/PD-L1) signaling axis are approved to treat non-small cell lung cancer (NSCLC) patients, based on their significant overall survival (OS) benefit. Using transcriptomic analysis of 891 NSCLC tumors from patients treated with either the PD-L1 inhibitor atezolizumab or chemotherapy from two large randomized clinical trials, we found a significant B cell association with extended OS with PD-L1 blockade, independent of CD8+ T cell signals. We then derived gene signatures corresponding to the dominant B cell subsets present in NSCLC from single-cell RNA-seq data. Importantly, we found increased plasma cell signatures to be predictive of OS in patients treated with atezolizumab, but not chemotherapy. B cells were also associated with the presence of tertiary lymphoid structures and organized lymphoid aggregates. Our results suggest an important contribution of B and plasma cells to PD-L1 blockade efficacy in NSCLC.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001007703 unspecified 891
EGAD00001008390 -
EGAD00001008391 -
EGAD00001008548 -
EGAD00001008549 -
EGAD00001008550 -
EGAD00001008628 -
EGAD00001008629 -
EGAD00001008630 -
EGAD00001008631 -
Publications Citations
Machine learning-based risk model incorporating tumor immune and stromal contexture predicts cancer prognosis and immunotherapy efficacy.
iScience 26: 2023 107058