B-cell-specific checkpoint molecules that regulate anti-tumour immunity

Lloyd Bod,et al.

The role of B cells in anti-tumour immunity is still debated and,accordingly,immunotherapies have focused on targeting T and natural killer cells to inhibit tumour growth1,2.Here,using high-throughput flow cytometry as well as bulk and single-cell RNA-sequencing and B-cell-receptor-sequencing analysis of B cells temporally during B16F10 melanoma growth,we identified a subset of B cells that expands specifically in the draining lymph node over time in tumour-bearing mice.The expanding B cell subset expresses the cell surface molecule T cell immunoglobulin and mucin domain 1 (TIM-1,encoded by Havcr1) and a unique transcriptional signature,including multiple co-inhibitory molecules such as PD-1,TIM-3,TIGIT and LAG-3.Although conditional deletion of these co-inhibitory molecules on B cells had little or no effect on tumour burden,selective deletion of Havcr1 in B cells both substantially inhibited tumour growth and enhanced effector T cell responses.Loss of TIM-1 enhanced the type 1 interferon response in B cells,which augmented B cell activation and increased antigen presentation and co-stimulation,resulting in increased expansion of tumour-specific effector T cells.Our results demonstrate that manipulation of TIM-1-expressing B cells enables engagement of the second arm of adaptive immunity to promote anti-tumour immunity and inhibit tumour growth.