Re-analysis of single cell and spatial transcriptomics data reveals B cell landscape in gastric cancer microenvironment and its potential crosstalk with tumor cells for clinical prognosis

• Published in: Journal of translational medicine 2024-08, Vol.22 (1), p.807-18, Article 807
• Main Authors: Cai, Xing, Yang, Jinru, Guo, Yusheng, Yu, Yanchao, Zheng, Chuansheng, Dai, Xiaofang
• Format: Article
• Language: English
• Subjects: Analysis; Animals; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Care and treatment; CCL28-CCR10; Cell Communication; Cell differentiation; Diagnosis; Gastric cancer; Gene Expression Profiling; Health aspects; Humans; Immunotherapy; LAMA/CD44; Mice; Patient outcomes; Prognosis; RNA sequencing; Single cell RNA sequencing; Single-Cell Analysis; Spatial transcriptome; Stomach cancer; Stomach Neoplasms - genetics; Stomach Neoplasms - immunology; Stomach Neoplasms - pathology; Transcriptome - genetics; Tumor Microenvironment - immunology
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-024-05606-9

At present, immunotherapy has become a powerful treatment for advanced gastric cancer (AGC), but not all patients can benefit from it. According to the latest research, the impact of B cell subpopulations on the immune microenvironment of gastric cancer (GC) is unknown. Exploring whether the interaction between B cells and tumor cells in GC affects the effectiveness of immunotherapy has attracted our interest. This study involved the re-analysis of single-cell RNA (scRNA) and spatial transcriptomics (ST) data from publicly available datasets. The focus was on investigating the subpopulations and differentiation trajectories of B cells in the gastric cancer (GC) tumor immune microenvironment (TIME). Spatial transcriptomics (ST) and multiple immunofluorescence (mIF) revealed a clear co-localization pattern between B cells and tumor cells. Multiple immunotherapy datasets were collected to identify unique immunotherapy biomarkers. The unique immunotherapeutic potential of targeting CCL28 was validated through a mouse gastric cancer model. In addition, flow cytometry revealed changes in the tumor immune microenvironment targeting CCL28. The re-analysis of ST data from multiple cancer types revealed a co-localization pattern between B cells and tumor cells. A significant number of IgA plasma cells were identified in the GC TIME. Five different tumor-infiltrating B cell subpopulations and two unique B cell differentiation trajectories were characterized, along with seven GC-related states. By analyzing the communication between GC cells and B cells, it was further discovered that tumor cells can influence and recruit plasma cells through CCL28-CCR10 signaling. Additionally, there was a crosstalk between GC cells and B cells. Finally, we identified the LAMA/CD44 signaling axis as a potential prognostic marker for immunotherapy through a large amount of immunotherapy data. We also validated through various animal tumor models that targeting CCL28 can significantly promote CD8 T cell infiltration and function in the TME by regulating B cell and plasma cell functions, and has the ability to synergize immunotherapy. The co-localization and crosstalk between GC cells and B cells significantly affect the efficacy of immunotherapy, and inhibiting the CCL28-CCR10 signal axis is a potential immunotherapy target for GC. Meanwhile, LAMA/CD44 pair may be a potential adverse indicator for immunotherapy and tumor prognosis.