一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CSDE1 depletion inhibits tumor progression through enhancing B-cell infiltration in NSCLC.
CSDE1 depletion inhibits tumor progression through enhancing B-cell infiltration in NSCLC.
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尽管大多数免疫治疗研究聚焦于 T 细胞,但越来越多的证据凸显了肿瘤浸润 B 淋巴细胞(TIL-Bs)在癌症治疗中的重要作用。CSDE1 已被认为与多种癌症和免疫反应相关。
本研究探讨 CSDE1 在肺癌进展中的作用及其对肿瘤免疫微环境的影响。我们发现 CSDE1 在体内促进肺癌进展,但在体外则不然。利用 Csde1 敲除的荷瘤小鼠模型,我们证明 Csde1 缺失显著抑制了肿瘤生长。单细胞 RNA 测序显示,Csde1 敲除重塑了肿瘤免疫微环境,尤其是显著增加了 TIL-B 水平,这一发现经流式细胞术和免疫荧光证实。
此外,Csde1 敲除增强了 B 细胞介导的体液免疫。值得注意的是,在 Csde1 敲除小鼠中清除 B 细胞逆转了 Csde1 缺失对肿瘤进展的抑制作用,凸显了 B 细胞在此过程中的关键作用。这些发现表明,CSDE1 通过调节 TIL-Bs 及更广泛的免疫微环境促进肿瘤进展。
本研究为肿瘤免疫治疗提供了新的潜在靶点和有价值的见解,强调了 B 细胞在癌症治疗策略中的重要性。
Although most immunotherapy research focuses on T cells, increasing evidence highlights the significant role of tumor-infiltrating B lymphocytes (TIL-Bs) in cancer therapy. CSDE1 has been implicated in various cancers and immune responses.
This study investigates the role of CSDE1 in lung cancer progression and its impact on the tumor immune microenvironment.
We found that CSDE1 promotes lung cancer progression in vivo but not in vitro. Using the tumor-bearing mice model with Csde1 knockout, we demonstrated that Csde1 deletion significantly inhibited tumor growth. Single-cell RNA sequencing revealed that Csde1 knockout reshaped the tumor immune microenvironment, particularly by significantly increasing TIL-B levels, a finding confirmed by flow cytometry and immunofluorescence.
Moreover, Csde1 knockout enhanced B-cell-mediated humoral immunity.
Notably, depleting B cells in Csde1 knockout mice reversed the inhibitory effect of Csde1 deletion on tumor progression, underscoring the critical role of B cells in this process.
These findings suggest that CSDE1 facilitates tumor progression by modulating TIL-Bs and the broader immune microenvironment.
This study provides a new potential target and valuable insights into tumor immunotherapy, emphasizing the importance of B cells in cancer treatment strategies.
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