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陈红, 胡翔, 张惠媛, 等. 三级淋巴器官（TLO）诱导形成及其在抗肿瘤免疫中的功能研究[J]. koko体育app 学报（医学版）, 2022, 53(1): 35-42. DOI:
引用本文: 陈红, 胡翔, 张惠媛, 等. 三级淋巴器官（TLO）诱导形成及其在抗肿瘤免疫中的功能研究[J]. koko体育app 学报（医学版）, 2022, 53(1): 35-42. DOI:
CHEN Hong, HU Xiang, ZHANG Hui-yuan, et al. Induction and Anti-Tumor Function of Tertiary Lymphoid Organs[J]. Journal of Sichuan University (Medical Sciences), 2022, 53(1): 35-42. DOI:
Citation: 𒆙 CHEN Hong, HU Xiang, ZHANG Hui-yuan, et al. Induction and Anti-Tumor Function of Tertiary Lymphoid Organs[J]. Journal of Sichuan University (Medical Sciences), 2022, 53(1): 35-42. DOI:

三级淋巴器官（TLO）诱导形成及其在抗肿瘤免疫中的功能研究

Induction and Anti-Tumor Function of Tertiary Lymphoid Organs

  • 摘要:
      目的   在体外诱导形成三级淋巴器官（tertiary lymphoid organs, TLO），并评价其在抗肿瘤免疫中的功能。
      方法   利用慢病毒系统在NIH3T3细胞上过表达淋巴毒素-β受体（lymphotoxin-beta receptor, LTβR），并检测LTβR-NIH3T3细胞中LTβR的过表达效率；通过免疫印迹实验和qPCR探究过表达LTβR的NIH3T3细胞内非经典核因子（nuclear factor, NF）-κB信号通路的情况。构建B16-OVA黑色素瘤小鼠荷瘤模型，探究LTβR-NIH3T3细胞诱导TLO形成的能力及抗肿瘤效果。
      结果   利用慢病毒感染在NIH3T3细胞中过表达LTβR，流式检测发现GFP+细胞比例达99%。过表达LTβR能在NIH3T3细胞内激活非经典NF-κB信号通路。小鼠肿瘤模型结果表明，注射LTβR-NIH3T3细胞能在肿瘤附近诱导形成淋巴样组织，并促进了T细胞和MHCⅡ+巨噬细胞的浸润，明显抑制荷瘤小鼠的肿瘤生长，并延长小鼠生存期。
      结论   LTβR-NIH3T3细胞通过诱导TLO的形成，促进抗肿瘤免疫，为肿瘤免疫治疗提供新的思路。
     
    Abstract:
      Objective  To induce the development of tertiary lymphoid organs (TLO) in a mouse model of melanoma and to evaluate TLO’s functions in antitumor immunity.
      Methods  Lymphotoxin-beta receptor (LTβR) was overexpressed in NIH3T3 cells through the lentivirus system and the overexpression efficiency of LTβR in LTβR-NIH3T3 cells was examined. Western blot and qPCR were used to examine the non-canonical nuclear factor (NF)-κB signaling pathway in NIH3T3 cells overexpressing LTβR. B16-OVA melanoma mouse model was constructed to explore the induction of TLO and anti-tumor functions of TLO in LTβR-NIH3T3 cells.
      Results  LTβR was overexpressed in NIH3T3 cells through the lentivirus system, and flow cytometry showed that the proportion of GFP+ cells reached 99%. The overexpression of LTβR activated the non-canonical NF-κB signaling pathway in NIH3T3 cells. Findings from the mouse tumor model suggest that the injection of LTβR-NIH3T3 cells successfully induced the development of lymphoid tissue around the tumor and enhanced the tumor infiltration of T cells and MHCⅡ+ macrophages, significantly inhibiting tumor growth and prolonging the survival of tumor-bearing mice.
      Conclusion  LTβR-NIH3T3 cells promoted anti-tumor immunity by inducing TLO development, which may provide new perspectives for tumor immunotherapy.
     
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