Single-cell profiling of infiltrating B cells and tertiary lymphoid structures in the TME of gastric adenocarcinomas

Abstract

The occurrence and development of gastric adenocarcinoma (gADC) is closely related to the interaction between tumor cells and immune cells in the tumor microenvironment (TME). Our objective was to characterize the repertoire of immune cells in the TME of gADC. To analyze the transcriptomic, immune, and spatial information of TME in gADC, we constructed single-cell RNA sequencing, 10 × Genomics V(D)J analysis, multiple immunofluorescence techniques, and OSCmap analysis of 49,765 single cells in seven samples from four gADC patients. Our integrative analysis of B cells demonstrated that a large number of mucosal associated lymphoid tissue (MALT)-B cells were detected in the gADC tissues, which have mature tertiary lymphatic structures (mTLSs), and almost no MALT-B cells in peripheral blood sample. Moreover, MALT-B cells are a class of IgA + plasma cells, which are characterized with high expression of complement pathway activation-related genes. Next, natural killer T (NKT) cells mainly exist in gADC tissues accompanied by mTLSs. This study also classified monocytes/macrophages and epithelial cells into benign and malignant types. Interestingly, CSOmap ( q < .05) and multiple immunofluorescence ( p < .05) results indicated more types of immune cells can be enriched in tissues with mTLSs than normal TLSs, and the density of mTLSs were higher than normal TLSs. Our findings provide novel insights for the signature of immune cells and tumor cells in the TME of gADC with TLSs and highlight the potential importance of IgA-mediated humoral immunity in gADC patients with TLSs.

Focal Adhesion-Related Signatures Predict the Treatment Efficacy of Chemotherapy and Prognosis in Patients with Gastric Cancer

“…Recently, the development of single-cell sequencing technology has enabled the analysis of tumor microenvironmental components at a higher resolution ( 35 , 36 ). A variety of cell subpopulations have been identified in GC, and these subpopulations exhibit completely different biological and immunological functions, thus revealing the high complexity of the microenvironment ( 37 , 38 ). In addition, studies on a variety of tumors have also suggested that different types of cancer may have similar immune cell types, but their proportions are different ( 36 ).…”

Discovering Immune-Mediated Mechanisms of Gastric Carcinogenesis Through Single-Cell RNA Sequencing

“…ScRNAseq analysis by Li et al (2022) reveals T cells as the most highly enriched immune cell population in the tumor microenvironment (TME), and their ratio increases as the disease advances (24). A greater diversity of unique T cell subsets and T cell receptor (TCR) repertoire were identified within tumor tissues when compared with that of patient-matched healthy tissue or peripheral blood mononuclear cells (PBMCs), suggesting that a variety of unique T cells infiltrate the TME (22). The main subsets of T cells that show infiltration into the TME in gastric cancer scRNAseq datasets include CD4 + T helper cells (Th, co-expressing CD4), CD8 + cytotoxic T lymphocytes (CTL, coexpressing CD8A), regulatory T cells (Treg, co-expressing FOXP3), and natural killer T cells (NKT, co-expressing NKG7) (20,22,26,39).…”

“…A greater diversity of unique T cell subsets and T cell receptor (TCR) repertoire were identified within tumor tissues when compared with that of patient-matched healthy tissue or peripheral blood mononuclear cells (PBMCs), suggesting that a variety of unique T cells infiltrate the TME (22). The main subsets of T cells that show infiltration into the TME in gastric cancer scRNAseq datasets include CD4 + T helper cells (Th, co-expressing CD4), CD8 + cytotoxic T lymphocytes (CTL, coexpressing CD8A), regulatory T cells (Treg, co-expressing FOXP3), and natural killer T cells (NKT, co-expressing NKG7) (20,22,26,39). Among these infiltrated subsets, some T cells have been implicated in a tumor-promoting role and others in a tumorinhibiting role.…”

“…Among the published scRNAseq gastric cancer works, it is apparent that they have undertaken various approaches to their studies. Most groups obtained primary gastric cancer tissues from patients to generate scRNAseq data (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Some utilized previously published primary tumor datasets for further analysis (36)(37)(38)(39)(40)(41)(42)(43).…”

A Dynamic Transcriptome Map of Different Tissue Microenvironment Cells Identified During Gastric Cancer Development Using Single-Cell RNA Sequencing

“…GC development undergoes a multi-stage process, from no-atrophic-gastritis (NAG) to chronic atrophic gastritis (CAG) to intestinal metaplasia (IM), and finally GC ( 2 ). During this process, gastric mucosa tissue and the tissue microenvironment (TME) undergo dynamic changes ( 3 ). The TME includes a variety of cell types (immune cells, fibroblasts, endothelial, etc.)…”