目前，免疫疗法已成为晚期胃癌（AGC）的有力治疗方法，但并非所有患者都能从中受益。最新研究表明，B细胞亚群对胃癌（GC）免疫微环境的影响尚不清楚。探索 GC 中 B 细胞和肿瘤细胞之间的相互作用是否影响免疫治疗的有效性引起了我们的兴趣。这项研究涉及对来自公开数据集的单细胞 RNA (scRNA) 和空间转录组 (ST) 数据的重新分析。重点研究胃癌（GC）肿瘤免疫微环境（TIME）中B细胞的亚群和分化轨迹。空间转录组学 (ST) 和多重免疫荧光 (mIF) 揭示了 B 细胞和肿瘤细胞之间清晰的共定位模式。收集多个免疫治疗数据集以识别独特的免疫治疗生物标志物。通过小鼠胃癌模型验证了靶向 CCL28 的独特免疫治疗潜力。此外，流式细胞术揭示了针对CCL28的肿瘤免疫微环境的变化。对多种癌症类型的ST数据的重新分析揭示了B细胞和肿瘤细胞之间的共定位模式。 GC TIME 中鉴定出大量 IgA 浆细胞。表征了五种不同的肿瘤浸润 B 细胞亚群和两种独特的 B 细胞分化轨迹，以及七种 GC 相关状态。通过分析GC细胞和B细胞之间的通讯，进一步发现肿瘤细胞可以通过CCL28-CCR10信号传导影响和招募浆细胞。此外，GC 细胞和 B 细胞之间存在串扰。最后，我们通过大量的免疫治疗数据，确定了LAMA/CD44信号轴作为免疫治疗的潜在预后标志物。我们还通过多种动物肿瘤模型验证，靶向CCL28可以通过调节B细胞和浆细胞功能，显着促进CD8 T细胞在TME中的浸润和功能，并具有协同免疫治疗的能力。GC细胞和GC细胞之间的共定位和串扰B细胞显着影响免疫治疗的疗效，抑制CCL28-CCR10信号轴是GC的潜在免疫治疗靶点。同时，LAMA/CD44 对可能是免疫治疗和肿瘤预后的潜在不利指标。© 2024。作者。

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.© 2024. The Author(s).