Good prognosis in patients with gastric adenocarcinoma correlates with IgA+ Tertiary Lymphoid Structures

Abstract The roles of tumor infiltrating B lymphocytes (TIBs) and tertiary lymphoid structures (TLSs) in solid tumor genesis and anti-tumor therapy have been recognized by researchers, but the specific formation and effect of TLSs have not been fully understood. In this study, single-cell RNA sequencing, multiple immunofluorescence assays, and cellular spatial organization mapper analysis were used to explore the structures of TLSs in gastric adenocarcinoma (GADC). Furthermore, the relationships between TLSs and clinicopathological characteristics and prognosis of GADC patients were analyzed. The results identified the phenotype of immunoglobulin A (IgA)+-TLSs which contained higher level of IgA+ plasma cells in GADC, and several types of immune cells in IgA+-TLSs had higher levels of cellular interactions and migration ability. Furthermore, IgA+-TLSs correlated with age, differentiation, distant metastasis, TNM stage, expression of programmed death-ligand 1, J-chain, SSR4, and good overall survival. In conclusion, IgA+ plasma cells higher expressed in IgA+-TLSs, and the formation of IgA+-TLSs promotes a better prognosis for GADC patients.