肿瘤微环境刚性的病机探讨

Pathogenesis of Tumor Microenvironment Stiffness

肿瘤硬度增加与临床触诊的常识相符,“积聚”“岩”病名即源于此。正虚则为岩,正气亏虚、脾运失健、肿瘤微环境中细胞外基质(ECM)的过量沉积及其组织形式的异常形成“有形之痰”,并与瘀血相搏、凝结蓄积甚或流毒走窜为患。肿瘤相关成纤维细胞的持续活化诱导ECM重塑和胶原蛋白的交联,基底膜与间质基质重构,导致“痰挟瘀血,遂成窠囊”。刚性微环境募集髓源抑制细胞和肿瘤相关巨噬细胞形成免疫抑制状态,抑制细胞毒性T淋巴细胞在肿瘤附近聚集体现“因实致虚”。肿瘤刚性微环境以正虚为本,痰瘀交结为标,应用扶正化瘀散结法调控机械力信号与ECM重构,降低肿瘤微环境硬度以改善免疫微环境,是软坚散结法调控肿瘤免疫的新思路。

The tumor stiffness fits in with the common sense of clinical examination.The rigidity of tumor mass or lump suggests the increased density of cancerous lesions.The deficiency of healthy Qi is essential for neoplasm formation.The abnormal arrangement and accumulation of extracellular matrix(ECM)lead to visible lump by dysfunction of Spleen.The tumorous mass induces migration and invation.Cancer-associated fibroblasts(CAFs)cause remodelling of basement membrane and stomal matrix by reconstructing ECM and collagen.CAFs upregulate tumor stiffness and interstitial fluid pressure and recruit myeloid-derived suppressor cells and tumor-associated macrophages.Phlegm and blood stasis entangle to form immunosuppressive microenvironment which inhibits the accumulation of cytotoxic T cells at the vicinity of tumor.Strengthening Qi,dissipating blood stasis and resolving hard lump maybe an efficacious strategy to soften immune microenvironment by regulating mechanical signaling and ECM remodeling.