Obeagu Emmanuel Ifeanyi
Department of Biomedical and Laboratory Science, Africa University, Mutare, Zimbabwe.
Department of Medical Laboratory Science, Kampala International University, Kampala, Uganda.
Cancer Manag Res. 2025 Jun 13;17:1113-1126. doi: 10.2147/CMAR.S527913. eCollection 2025.
Cervical cancer progression is not solely driven by persistent human papillomavirus (HPV) infection but is profoundly influenced by the local immune microenvironment, particularly chronic cytokine imbalances. Unlike the acute cytokine storms observed in infections or sepsis, cervical cancer is characterized by a persistent, low-grade, "smoldering inflammatory response" that fuels tumor initiation, progression, and immune evasion. Pro-inflammatory cytokines such as IL-6, IL-1β, TNF-α, and IL-8 sustain a tumor-supportive milieu, promoting angiogenesis, epithelial-mesenchymal transition, and resistance to apoptosis, while immunosuppressive cytokines like IL-10 and TGF-β dampen anti-tumor immune responses and facilitate immune escape. This review explores chronic cytokine dysregulation in cervical cancer, examining how the prolonged, dysregulated cytokine network shapes the tumor microenvironment, remodels stromal interactions, and influences immune cell recruitment and function. We highlight key cytokines involved in these processes and discuss their clinical significance as potential diagnostic, prognostic, and predictive biomarkers. Understanding these sustained inflammatory processes is critical because they represent a distinct biological landscape compared to acute inflammatory reactions and offer unique windows for therapeutic intervention. The paper reviewed emerging therapeutic strategies targeting these chronic cytokine pathways, including cytokine blockade, immune modulation, and combination approaches integrating immunotherapies or nanomedicine. Addressing chronic cytokine dysregulation holds promise for improving cervical cancer management and patient outcomes.
宫颈癌的进展并非仅由持续性人乳头瘤病毒（HPV）感染驱动，还受到局部免疫微环境的深刻影响，尤其是慢性细胞因子失衡。与感染或脓毒症中观察到的急性细胞因子风暴不同，宫颈癌的特征是持续的、低度的“隐匿性炎症反应”，这种反应促进肿瘤的起始、进展和免疫逃逸。促炎细胞因子如IL-6、IL-1β、TNF-α和IL-8维持肿瘤支持性微环境，促进血管生成、上皮-间质转化和抗凋亡能力，而免疫抑制细胞因子如IL-10和TGF-β则抑制抗肿瘤免疫反应并促进免疫逃逸。本综述探讨了宫颈癌中慢性细胞因子失调，研究了长期失调的细胞因子网络如何塑造肿瘤微环境、重塑基质相互作用以及影响免疫细胞募集和功能。我们强调了参与这些过程的关键细胞因子，并讨论了它们作为潜在诊断、预后和预测生物标志物的临床意义。了解这些持续的炎症过程至关重要，因为它们代表了与急性炎症反应不同的独特生物学格局，并为治疗干预提供了独特的窗口。本文综述了针对这些慢性细胞因子途径的新兴治疗策略，包括细胞因子阻断、免疫调节以及整合免疫疗法或纳米医学的联合方法。解决慢性细胞因子失调有望改善宫颈癌的管理和患者预后。
