决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Angiogenesis-related gene NID2 profiling and immune infiltration in bladder cancer: prognostic implications and immunotherapy response.
我们的研究成功识别了BC患者中与预后相关的AAG特征。这些特征不仅有助于更清晰地理解TME属性,也为探索更有效的免疫治疗策略提供了重要依据。
免疫治疗已逐步成为多种肿瘤治疗场景中的基石性治疗手段,其临床疗效与肿瘤微环境(TME)和肿瘤细胞之间的动态相互作用密切相关。在这一范式中,血管生成处于核心地位——作为癌症的基本标志之一,它不仅维持肿瘤生长,还调控TME内的免疫调节网络,从而深刻影响治疗反应性。然而,在膀胱癌(BC)领域,血管生成与预后、免疫治疗反应及免疫细胞浸润之间的关系仍有待进一步探索。
为了系统性地揭示这一关系,我们对36个与血管生成相关的基因(AAGs)进行了详尽的评估,并探讨了血管生成与转录本、预后结局以及免疫细胞浸润之间的关系。通过构建AAG_score,我们量化了每位患者的血管生成亚型特征。随后,我们评估了这些特征在预测BC预后和治疗反应中的价值,同时分析了AAGs在弥漫性大B细胞淋巴瘤中的表现以进行比较研究。通过RT-qPCR、CCK8及其他实验,我们验证了NID2在膀胱癌中的作用。
本研究在基因水平上探索了BC样本中不同类型的AAGs突变,并阐明了AAGs的表达模式。通过深入分析,我们识别出两个不同的分子亚群,并发现AAG突变与患者的临床病理特征、预后及侵袭性TME之间存在显著关联。我们发现AAG_score低的患者表现出微卫星不稳定性增加、高突变倾向和免疫激活,且预后更好。NID2在膀胱癌中发挥促进增殖的作用,并在弥漫性大B细胞淋巴瘤中进行了评估。此外,我们的研究发现,在药物敏感性方面,癌症干细胞指数与AAG_score之间存在显著相关性。
BACKGROUND: Immunotherapy has progressively gained prominence as a cornerstone therapeutic modality across diverse oncological contexts, with its clinical efficacy intricately linked to the dynamic interactions between the tumor microenvironment (TME) and neoplastic cells. Central to this paradigm is angiogenesis-a quintessential hallmark of cancer-which not only sustains tumor growth but also orchestrates immunomodulatory networks within the TME, thereby profoundly influencing therapeutic responsiveness. However, in the field of bladder cancer (BC), the relationship among angiogenesis and prognosis, immunotherapy response, and immune cell infiltration remains to be further explored. METHODS: To systematically uncover this relationship, we carried out an exhaustive assessment of 36 genes linked to angiogenesis (AAGs) and explored the relationship between angiogenesis and transcript, prognostic outcomes, as well as the infiltration of immune cells. By constructing an AAG_score, we quantified the angiogenic subtype characteristics of each patient. Subsequently, we evaluated the value of these characteristics in foreseeing BC prognosis and the response of treatment, and concurrently analyzed the performance of AAGs in diffuse large B-cell lymphoma for comparative study. Through RT-qPCR, CCK8 and other experiments, we verified the role of NID2 in bladder cancer. RESULTS: This study explored different types of AAGs mutations in BC samples at the genetic level and elucidated the expression patterns of AAGs. Through in-depth analysis, we identified two distinct molecular subpopulations and found significant associations between AAG mutations and patients' clinicopathological features, prognosis, and invasive TME. We found that patients with low AAG_score showed increased microsatellite instability, high mutation tendency, and immune motivation, and had a better prognosis. NID2 plays a role in promoting proliferation in bladder cancer and evaluate in diffuse large B-cell lymphoma. In addition, our study found a significant correlation between index of cancer stem cell and AAG_score in drug sensitivity. CONCLUSION: In summary, our study successfully identified prognosis-related AAG characteristics in BC patients. These characteristics not only contribute to a clearer understanding of TME properties but also provide an important basis for exploring more effective immunotherapy strategies.
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