论文分享 | 联科流式抗体助力胶质母细胞瘤的免疫治疗研究

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2024年3月9日，中国武汉大学中南医院放射科Tianliang Li ，Haibo Xu等老师在Advanced Science（IF=15.1）上，在线发表题为“Metabolism/Immunity Dual-Regulation Thermogels Potentiating Immunotherapy of Glioblastoma Through Lactate-Excretion Inhibition and PD-1/PD-L1 Blockade”的论文，此论文使用了联科生物Anti-Mouse CD274(PD-L1,B7-H1), APC (Clone: 10F.9G2)检测试剂(货号:F2127403），Anti-Mouse CD80 (B7-1), PE (Clone:16-10A1)检测试剂(货号:F2108002），Anti-Mouse CD45, PE (Clone:30-F11)检测试剂(货号:F2104502），Anti-Mouse CD45, FITC (Clone:30-F11)检测试剂(货号:F2104501），Anti-Human/Mouse CD11b, PerCP-Cy5.5 (Clone: M1/70)检测试剂(货号:F41011b04），Anti-Mouse CD3ε, PerCP-Cy5.5 (Clone:145-2C11)检测试剂(货号:F2100304），Anti-Mouse CD4, FITC (Clone:GK1.5)检测试剂(货号:F2100401），Anti-Mouse FoxP3, APC (Clone:3G3)检测试剂(货号:F21FP303），Anti-Mouse IFN-γ, APC (Clone:XMG1.2)检测试剂(货号:F21IFNG03），Anti-Mouse MHC Class II (I-A/I-E), FITC (Clone:M5/114.15.2)检测试剂(货号:F21IIAE01）。

Gel@B-B combined with tumor vaccine enhanced immunotherapy effect of GBM. A) Treatment schedule of orthotopic GBM mice in situ injection of Gel and Gel@B-B. B) Image of LNs from mice subcutaneously injected with or without GBM vaccine. C,D) FCM examination and quantitative analysis of DC maturation (CD80CD86 gated in CD45CD11c) in LNs (n = 3). E) Tumor of mice imaged by MRI system. F) Survival of mice within 60 days (p = 0.0250, n = 6). G) Immunofluorescence sections of tumor tissues were stained with DAPI (blue) and CD3 (green), scale bar 50 µm. H–M) FCM examination and quantitative analysis of T cells (CD3 gated in CD45), Th1 (IFN-γCD4 in CD3), and CTLs (IFN-γCD8 in CD3), n = 3. N–P) ELISA analysis of the intratumoral secretion of TNF-α, IFN-γ, and TGF-β (n = 3). Data are means ± SD, and statistical significance was calculated by t-test. p < 0.05, p < 0.01, p < 0.001.******

肿瘤内在免疫抑制微环境（ITM）和T细胞对肿瘤的不足浸润严重阻碍了胶质母细胞瘤（GBM）免疫疗法的进展。研究发现，抑制葡萄糖转运蛋白1（GLUT1）的表达可以促进阻止肿瘤糖酵解产生乳酸的过程，从而显著减轻了乳酸驱动的ITM，降低了免疫抑制性的肿瘤相关巨噬细胞（TAMs）和调节性T细胞（Tregs）。同时，研究结果显示，免疫激活过程中产生的炎症细胞因子IFN-γ通过上调肿瘤细胞和TAMs的免疫检查点程序化死亡配体1（PD-L1），加重了免疫逃逸。因此，开发了一种注射用热凝胶，载有GLUT1抑制剂BAY-876和PD-1/PD-L1阻断剂BMS-1（Gel@B-B），用于GBM的代谢和免疫双重调节。结果显示，在原位注射Gel@B-B显著延缓了肿瘤生长，并延长了正位GBM小鼠模型的生存期。通过将肿瘤抗原主动暴露给抗原呈递细胞，发现GBM疫苗与Gel@B-B联合应用能显著增加肿瘤微环境中效应T细胞（Th1/CTLs）的比例，从而明显减轻了肿瘤的长期复发。这项研究可能为GBM免疫疗法提供了一种有前景的策略。

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流式抗体部分引用文献

1、Che YJ, Ren XH, Wang ZW, et al. Lymph-Node-Targeted Drug Delivery for Effective Immunomodulation to Prolong the Long-Term Survival After Heart Transplantation. Adv Mater. 2023;35(16):e2207227.

2、Shang, Yunkai et al.Bioengineered Nanospores Selectively Blocking LC3-Associated Phagocytosis in Tumor-Associated Macrophages Potentiate Antitumor Immunity. ACS nano vol. 17,11 (2023): 10872-10887.

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参考文献：
Li T, Xu D, Ruan Z, et al. Metabolism/Immunity Dual-Regulation Thermogels Potentiating Immunotherapy of Glioblastoma Through Lactate-Excretion Inhibition and PD-1/PD-L1 Blockade. Adv Sci (Weinh). Published online March 9, 2024.

原文链接：https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202310163