Single cell profiling of bronchoalveolar immune cells in checkpoint inhibitor-related pneumonitis

Abstract Immune checkpoint inhibitors (ICIs) therapy induced pneumonitis (CIP) complicates this effective in therapy patients with non-small cell lung cancer (NSCLC), but the underlying mechanisms remain incompletely understood. Here, we implemented comprehensive single-cell transcriptome, flow cytometry and cytokine expression analysis to shed light on the complexity of the immunological responses in the bronchoalveolar microenvironment from NSCLC patients with CIP. We demonstrated a dramatic accumulation of CXCL13+ CD4 and CD8 T cells with highly cytotoxic and effector functions in CIP. Monocyte differentiation trajectories showed that hyperinflammatory monocytes and LAMP3+ dendritic cells (DCs) were enriched in CIP, while anti-inflammatory macrophages were depleted. Multilineages intercellular crosstalk analysis revealed that CIP specific myeloid subsets could recruit and enhance CXCL13+ T cells cytotoxic function through CXCL9/10-CXCR3 and IFNGR1/2-IFNG pathway, respectively. Together, our data highlighted the importance of CXCL13+ T cells and LAMP3+ DCs in CIP pathogenesis, which could be non-invasive biomarkers to monitor CIP.