Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Bod, L; Kye, YC; Shi, J; Torlai, Triglia, E; Schnell, A; Fessler, J; Ostrowski, SM; Von-Franque, MY; Kuchroo, JR; Barilla, RM; Zaghouani, S; Christian, E; Delorey, TM; Mohib, K; Xiao, S; Slingerland, N; Giuliano, CJ; Ashenberg, O; Li, Z; Rothstein, DM; Fisher, DE; Rozenblatt-Rosen, O; Sharpe, AH; Quintana, FJ; Apetoh, L; Regev, A; Kuchroo, VK.
B-cell-specific checkpoint molecules that regulate anti-tumour immunity.
Nature. 2023; 619(7969):348-356
Doi: 10.1038/s41586-023-06231-0
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- Co-Autor*innen der Med Uni Graz
- Fessler Johannes
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Mice - administration & dosage
- B-Lymphocytes - cytology, immunology, metabolism
- Lymphocyte Activation - administration & dosage
- Melanoma - immunology, pathology, prevention & control
- T-Lymphocytes - cytology, immunology
- Flow Cytometry - administration & dosage
- Melanoma, Experimental - immunology, pathology
- Lymph Nodes - cytology, immunology
- Antigen Presentation - administration & dosage
- Receptors, Antigen, B-Cell - genetics
- Single-Cell Gene Expression Analysis - administration & dosage
- Tumor Burden - administration & dosage
- Interferon Type I - administration & dosage