Zhang Leyi, Pan Jun, Chen Wuzhen, Jiang Jinxin, Huang Jian
Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310009, P. R. China.
Cancer Institute (Key Laboratory of Cancer Prevention & Intervention, National Ministry of Education; Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province), Second Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310009, P. R. China.
Am J Cancer Res. 2020 May 1;10(5):1294-1307. eCollection 2020.
Psychological stress is a well-accepted risk factor in cancer initiation and progression. The explosive growth of psychoneuroimmunology research in the past decade has yielded an unprecedented wealth of information about the critical role of chronic stress in the immune dysfunction that influences tumor behaviors, which presents insights to mitigate distress and improve prognosis in cancer patients. Chronic stress exacerbates inflammation and causes a metabolism disorder, making it difficult for the organisms to maintain homeostasis and increasing its susceptibility to cancer. The shifted differentiation and redistribution of the immune system induced by chronic stress fail to combat cancer efficiently. Chronic stress increases the tumor-educated immune suppressive cells and impairs the cytotoxicity of cellular immunity, thereby promoting lymphatic metastasis and hematogenous metastasis. In addition, the efficacy of existing cancer therapies is undermined because chronic stress prevents the immune system from responding properly. Emerging stress-reduction measures have been administered to assist cancer patients to cope with the adverse effects of chronic stress. Here we systematically review the current molecular, cellular, physiological mechanisms about stress-mediated immune responses in the enhancement of tumor initiation and progression, remodeling of tumor microenvironment and impairment of anti-tumor treatment. We also summarize the potential clinically applicable stress-oriented strategies towards cancer and discuss briefly where important knowledge gaps remain.
心理压力是癌症发生和发展中公认的风险因素。在过去十年中，心理神经免疫学研究的迅猛发展产生了前所未有的丰富信息，揭示了慢性压力在影响肿瘤行为的免疫功能障碍中的关键作用，这为减轻癌症患者的痛苦和改善预后提供了思路。慢性压力会加剧炎症并导致代谢紊乱，使机体难以维持内环境稳定，并增加其患癌易感性。慢性压力引起的免疫系统分化和重新分布的改变无法有效地对抗癌症。慢性压力会增加肿瘤诱导的免疫抑制细胞，并损害细胞免疫的细胞毒性，从而促进淋巴转移和血行转移。此外，由于慢性压力会阻碍免疫系统的正常反应，现有癌症治疗方法的疗效也会受到影响。目前已经采取了一些减轻压力的措施来帮助癌症患者应对慢性压力的不良影响。在此，我们系统地综述了当前关于压力介导的免疫反应在促进肿瘤发生发展、重塑肿瘤微环境和损害抗肿瘤治疗方面的分子、细胞和生理机制。我们还总结了针对癌症潜在的临床适用的压力导向策略，并简要讨论了重要的知识空白所在。
