CD19CD73 B cells infiltration indicates poor prognosis and unfavorable responses to immunotherapy in gastric cancer.

[OBJECTIVES] Cluster of Differentiation 73 (CD73) is expressed on immune cells and plays a significant role in tumor inhibition by suppressing antitumor immunity. The objectives of this study were to explore the expression and functional mechanisms of CD73 on B cells in patients with gastric cancer (GC).

[METHODS] The prognostic significance of CD19CD73 B cells was evaluated in 390 GC patients through dual immunohistochemistry staining. Flow cytometry was employed to analyze the phenotype of the CD19 subpopulation using fresh tumor and non-tumor tissue samples from 8 GC patients. A bioinformatics analysis of CD19CD73 B cells was also performed within the scRNA-seq cohort, and the CD19 B cell subtype was assessed using multiple immunofluorescence staining.

[RESULTS] The infiltration of CD19CD73 B cells was observed to be elevated in gastric cancer (GC) tissue compared to normal tissues. A strong correlation was observed between high CD19CD73 B cell infiltration, poor overall survival, and diminished responsiveness to neoadjuvant immunotherapy in GC. These cells emerged as a novel subset of regulatory B cells (Bregs) linked to adenosine metabolism and the exhaustion of CD8 T cells. The CD19CD73 B cells also correlated with the production of immunosuppressive cytokines IL-10 and TGFB1. Further analysis indicated an association between CD19CD73 B cells and advanced-stage GC.

[CONCLUSIONS] The presence of CD19CD73 B cells in GC may serve as a prognostic indicator for clinical outcomes and a predictive marker for poor responsiveness to neoadjuvant immunotherapy. The correlation between the presence of CD19CD73 B cells and CD8 T cell exhaustion, along with immunosuppression, highlights the tumor-promoting function of these cells.