Department of Medical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, No 789 Suzhou Road, Urumqi, 830011, Xinjiang, China.
Postdoctoral Research Workstation of Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, China.
Eur J Med Res. 2024 Jul 5;29(1):357. doi: 10.1186/s40001-024-01897-2.
PD-1/PD-L1 inhibitors have become a promising therapy. However, the response rate is lower than 30% in patients with cervical cancer (CC), which is related to immunosuppressive components in tumor microenvironment (TME). Tumor-associated macrophages (TAMs), as one of the most important immune cells, are involved in the formation of tumor suppressive microenvironment. Therefore, it will provide a theoretical basis for curative effect improvement about the regulatory mechanism of TAMs on PD-L1 expression.
The clinical data and pathological tissues of CC patients were collected, and the expressions of PD-L1, CD68 and CD163 were detected by immunohistochemistry. Bioinformatics was used to analyze the macrophage subtypes involved in PD-L1 regulation. A co-culture model was established to observe the effects of TAMs on the morphology, migration and invasion function of CC cells, and the regulatory mechanism of TAMs on PD-L1.
PD-L1 expression on tumor cells could predict the poor prognosis of patients. And there was a strong correlation between PD-L1 expression with CD163TAMs infiltration. Similarly, PD-L1 expression was associated with M1/M2-type TAMs infiltration in bioinformatics analysis. The results of cell co-culture showed that M1/M2-type TAMs could upregulate PD-L1 expression, especially M2-type TAMs may elevate the PD-L1 expression via PI3K/AKT pathway. Meanwhile, M1/M2-type TAMs can affect the morphological changes, and enhance migration and invasion abilities of CC cells.
PD-L1 expression in tumor cells can be used as a prognostic factor and is closely related to CD163TAMs infiltration. In addition, M2-type TAMs can upregulate PD-L1 expression in CC cells through PI3K/AKT pathway, enhance the migration and invasion capabilities, and affect the tumor progression.
PD-1/PD-L1 抑制剂已成为一种有前途的治疗方法。然而，在宫颈癌（CC）患者中的反应率低于 30%，这与肿瘤微环境（TME）中的免疫抑制成分有关。肿瘤相关巨噬细胞（TAMs）作为最重要的免疫细胞之一，参与肿瘤抑制微环境的形成。因此，研究 TAMs 对 PD-L1 表达的调控机制将为提高疗效提供理论依据。
收集 CC 患者的临床资料和病理组织，采用免疫组织化学法检测 PD-L1、CD68 和 CD163 的表达。采用生物信息学方法分析参与 PD-L1 调节的巨噬细胞亚型。建立共培养模型，观察 TAMs 对 CC 细胞形态、迁移和侵袭功能的影响，以及 TAMs 对 PD-L1 的调控机制。
肿瘤细胞上的 PD-L1 表达可预测患者的预后不良。并且 PD-L1 表达与 CD163TAMs 浸润之间存在很强的相关性。同样，在生物信息学分析中，PD-L1 表达与 M1/M2 型 TAMs 浸润相关。细胞共培养结果表明，M1/M2 型 TAMs 可上调 PD-L1 表达，尤其是 M2 型 TAMs 可能通过 PI3K/AKT 通路上调 PD-L1 表达。同时，M1/M2 型 TAMs 可影响 CC 细胞的形态变化，并增强其迁移和侵袭能力。
肿瘤细胞中的 PD-L1 表达可作为预后因素，与 CD163TAMs 浸润密切相关。此外，M2 型 TAMs 可通过 PI3K/AKT 通路上调 CC 细胞中的 PD-L1 表达，增强其迁移和侵袭能力，并影响肿瘤进展。
