Currently, a number of promising strategies and approaches to cancer treatment include differentiation therapy. However, theoretical and methodological foundations of this field are not yet well developed. The objective of this study was to determine the effects of a mixture of polyclonal activators (PAs; phytohaemagglutinin, concanavalin A and lipopolysaccharide) on cytokine production by biopsy samples of invasive breast carcinoma of no special type (IBC-NST) having various differentiation abilities and metastatic potentials as well as on differentiation status of the IBC-NST biopsy samples. We used ELISAs to investigate spontaneous and PA-stimulated cytokine production in the IBC-NST biopsy samples; from these data, we calculated a cytokine production stimulation index (SIPA). The effect of PAs on tumour cell differentiation was determined via a differentiation stimulation index (DSI). DSI was found to vary within the range 1.0–5.0. After treatment with PAs, in the IBC-NST biopsy samples of group I (DSI <1.25), the production of IL-2, IL-6, IL-8, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α and GM-CSF increased; in the biopsy samples of group II (DSI >1.25), the production of IL-6, IL-1β, IL-1Ra, TNF-α, G-CSF and GM-CSF significantly increased, while the production of VEGF-A decreased. Receiver operating characteristic (ROC) analysis of SIPA revealed that increased production of IL-18 in the IBC-NST biopsy samples after exposure to PAs may block the PA-driven, cytokine-mediated differentiation of moderately differentiated into highly differentiated tumour cells. The ROC analysis also uncovered an association between the responses of tumour cells to PAs and lymph node metastasis observed in the patients. The findings suggest that there is a need for research aimed at finding new drugs for differentiating cancer therapy and at searching for targeted inducers of cytokine production or specific suppressors of their induction.

目前，许多有前途的癌症治疗策略和方法包括分化疗法。然而，该领域的理论和方法基础尚未完善。本研究的目的是确定多克隆激活剂（PA；植物血凝素、刀豆球蛋白 A 和脂多糖）混合物对具有不同分化能力和不同分化能力的非特殊类型浸润性乳腺癌 (IBC-NST) 活检样本产生细胞因子的影响。转移潜力以及 IBC-NST 活检样本的分化状态。我们使用 ELISA 来研究 IBC-NST 活检样本中自发的和 PA 刺激的细胞因子产生；根据这些数据，我们计算了细胞因子产生刺激指数（SIPA）。PA 对肿瘤细胞分化的影响通过分化刺激指数 (DSI) 确定。发现 DSI 在 1.0–5.0 范围内变化。PAs治疗后，在I组（DSI <1.25）的IBC-NST活检样本中，产生IL-2、IL-6、IL-8、IL-17、IL-18、IL-1β、IL- 1Ra、TNF-α和GM-CSF升高；在第II组（DSI>1.25）的活检样本中，IL-6、IL-1β、IL-1Ra、TNF-α、G-CSF和GM-CSF的产生显着增加，而VEGF-A的产生减少。SIPA 的受试者工作特征 (ROC) 分析显示，暴露于 PA 后 IBC-NST 活检样本中 IL-18 的产生增加可能会阻止 PA 驱动、细胞因子介导的中度分化为高度分化的肿瘤细胞的分化。ROC 分析还揭示了肿瘤细胞对 PA 的反应与患者中观察到的淋巴结转移之间的关联。研究结果表明，需要进行旨在寻找用于差异化癌症治疗的新药以及寻找细胞因子产生的靶向诱导剂或其诱导的特异性抑制剂的研究。