Liu Chang, Xiao Zhuanglong, Du Li, Zhu Shenghua, Xiang Hongyu, Wang Zehui, Liu Fang, Song Yuhu
Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Cell Death Discov. 2023 Jan 23;9(1):25. doi: 10.1038/s41420-023-01312-5.
Type 1 T helper (Th1) cells generate an efficient antitumor immune response in multiple malignancies. The functions of Th1 cells in malignant ascites (MA) have not been elucidated. The distribution of helper T cells in peritoneal fluid and peripheral blood was determined in patients and animal models with malignant ascites. The effects of Th1-derived interferon-γ (IFN-γ) on the formation of malignant ascites were investigated. The mechanism underlying the recruitment of Th1 cells into peritoneal cavity was explored. In patients with malignant ascites and animal models of malignant ascites, the percentage of Th1 cells increased in peritoneal fluid compared with peripheral blood. Next, our experiment demonstrated that Th1 cells inhibited the growth of tumor cells by secreting IFN-γ in vitro. In murine models of malignant ascites, increased peritoneal fluid and shorter survival time were observed in IFN-γ mice compared with wild-type (WT) mice. Then, the levels of C-X-C motif chemokine ligand (CXCL) 9/10 and the ratio of CXCR3 Th1 cells indicated the involvement of CXCL9, 10/CXCR3 axis in the recruitment of Th1 cells into peritoneal cavity. As expected, in murine models of malignant ascites, the gradient between ascitic Th1 ratio and blood Th1 ratio decreased in CXCR3 mice compared with WT mice. IFN-γ secreted by recruited Th1 cells in peritoneal cavity inhibits the formation of malignant ascites. Hence, manipulation of Th1 cells or IFN-γ will provide a therapeutic candidate against malignant ascites.
1型辅助性T（Th1）细胞在多种恶性肿瘤中产生有效的抗肿瘤免疫反应。Th1细胞在恶性腹水（MA）中的功能尚未阐明。在患有恶性腹水的患者和动物模型中，测定了腹腔液和外周血中辅助性T细胞的分布。研究了Th1衍生的干扰素-γ（IFN-γ）对恶性腹水形成的影响。探讨了Th1细胞募集到腹腔的潜在机制。在恶性腹水患者和恶性腹水动物模型中，与外周血相比，腹腔液中Th1细胞的百分比增加。接下来，我们的实验表明，Th1细胞在体外通过分泌IFN-γ抑制肿瘤细胞的生长。在恶性腹水小鼠模型中，与野生型（WT）小鼠相比，IFN-γ小鼠的腹腔液增加且生存时间缩短。然后，C-X-C基序趋化因子配体（CXCL）9/10水平和CXCR3 Th1细胞比例表明CXCL9、10/CXCR3轴参与Th1细胞募集到腹腔。正如预期的那样，在恶性腹水小鼠模型中，与WT小鼠相比，CXCR3小鼠腹腔Th1比例与血液Th1比例之间的梯度降低。腹腔中募集的Th1细胞分泌的IFN-γ抑制恶性腹水的形成。因此，对Th1细胞或IFN-γ的调控将为恶性腹水提供一种治疗候选方案。
