AI Article Synopsis
- B lymphocytes play a crucial role in immune response and are involved in various aspects of cancer progression, exhibiting significant diversity with 15 identified subsets.
- A detailed analysis of tumor-infiltrating B cells across 20 cancer types revealed two key developmental pathways, with the extrafollicular pathway correlating with poorer clinical outcomes and immunotherapy resistance.
- The study suggests that the balance between extrafollicular and germinal-center B cell responses within tumors may be targeted to enhance immunotherapy efficiency, particularly through understanding their metabolic interactions.
Article Abstract
B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions of tumor-infiltrating B cells, we generated a B cell blueprint encompassing single-cell transcriptome, B cell-receptor repertoire, and chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). B cells harbored extraordinary heterogeneity and comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor types grouped into the extrafollicular pathway were linked with worse clinical outcomes and resistance to immunotherapy. The dysfunctional extrafollicular program was associated with glutamine-derived metabolites through epigenetic-metabolic cross-talk, which promoted a T cell-driven immunosuppressive program. These data suggest an intratumor B cell balance between extrafollicular and germinal-center responses and suggest that humoral immunity could possibly be harnessed for B cell-targeting immunotherapy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1126/science.adj4857 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!