Pi (Spleen)-deficiency syndrome in tumor microenvironment is the pivotal pathogenesis of colorectal cancer immune escape
Pi (Spleen)-deficiency syndrome in tumor microenvironment is the pivotal pathogenesis of colorectal cancer immune escape
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DOI：
10.1007/s11655-015-2086-5
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发表时间：
2016-10-01
影响因子：
2.9
通讯作者：
Li Kun
中科院分区：
文献类型：
--
作者：
Sun Xue-gang;Lin Xiao-chang;Li Kun
癌症免疫编辑包括三个连续的阶段：消除，平衡和逃逸。对于结直肠腺瘤-癌序列，腺瘤的不典型增生进展可能代表一个平衡期，而癌阶段可能代表逃逸期。免疫系统首先通过破坏转化的肠上皮细胞来消除它们，同时对其进行雕刻，随后选择不再被识别且对免疫效应物不敏感的变体，最终在肿瘤微环境中诱导免疫抑制状态，从而促进免疫逃逸和肿瘤生长。免疫抑制和炎症是脾虚的两个重要特征。经典语录、免疫学证据和临床观察表明，脾虚（而非其他器官）是结直肠癌（CRC）微环境的关键发病机制。年老体弱、慢性炎症产生的免疫抑制细胞因子、肿瘤源性免疫抑制因子和投降的免疫细胞-调节性T细胞、髓源性抑制细胞和肿瘤相关巨噬细胞（TAMs）构成了PI缺乏的CRC微环境。此外，在本虚免疫抑制的基础上，慢性炎症导致痰瘀毒结等标实。中医大师强调健脾是大肠癌的主要治疗原则，并收到良好的治疗效果。因此，脾虚为本证是肿瘤微环境的关键病机。免疫抑制微环境促进免疫逃逸，在腺瘤向腺癌转化过程中发挥重要作用。有一些迹象表明，加强基于Pi的治疗具有改善肿瘤环境的潜在能力。这可能是探讨加强Pi治疗通过调节肿瘤环境和免疫编辑防治结直肠癌的机制的一个新的切入点。
Cancer immunoediting consists of three sequential phases: elimination, equilibrium, and escape. For colorectal adenoma-carcinoma sequence, the adenoma dysplastic progression may represent an equilibrium phase and the cancer stage as escape phase. Immune system eliminates transformed enterocytes by destroying them at first, sculpts them at the same time and selects the variants subsequently that are no longer recognized and insensitive to immune effectors, and finally induces immunosuppressive state within the tumor microenvironment that facilitates immune escape and tumor outgrowth. Immunosuppression and inflammation are the two crucial features of Pi (Spleen)-deficiency. Classic quotations, immune evidence and clinical observations suggest that Spleen (but not other organs) deficiency is the key pathogenesis of colorectal cancer (CRC) microenvironment. Weakness of old age, immunosuppressive cytokines from chronic inflammation, tumor-derived immunosuppressive factors and surrendered immune cells-regulatory T cells, myeloid-derived suppressor cells and tumor associated macrophages (TAMs) constitutes CRC microenvironment of Pi-deficiency. Furthermore, excess in superficiality, such as phlegm stagnation, blood stasis and toxin accumulation are induced by chronic inflammation on the basis of asthenia in origin, an immunosuppressive state. Great masters of Chinese medicine emphasize that strengthen Pi is the chief therapeutic principle for CRC which receives good therapeutic effects. So, Pi-deficiency based syndrome is the pivotal pathogenesis of tumor microenvironment. The immunosuppressive microenvironment facilitates immune escape which play an important role in the transition from adenoma to adenocarcinoma. There are some signs that strengthen Pi based treatment has potential capacity to ameliorate tumor environment. It might be a novel starting point to explore the mechanism of strengthen Pi based therapy in the prevention and treatment of CRC through regulation of tumor environment and immunoediting.