Biobehavioral Cancer Control Program UPMC Hillman Cancer Center, Center for Neuroscience, Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA, USA.
Immunol Cell Biol. 2021 Oct;99(9):949-961. doi: 10.1111/imcb.12496. Epub 2021 Sep 12.
Evolutionarily, the nervous system and immune cells have evolved to communicate with each other to control inflammation and host responses against injury. Recent findings in neuroimmune communication demonstrate that these mechanisms extend to cancer initiation and progression. Lymphoid structures and tumors, which are often associated with inflammatory infiltrate, are highly innervated by multiple nerve types (e.g. sympathetic, parasympathetic, sensory). Recent preclinical and clinical studies demonstrate that targeting the nervous system could be a therapeutic strategy to promote antitumor immunity while simultaneously reducing cancer-associated neurological symptoms, such as chronic pain, fatigue and cognitive impairment. Sympathetic nerve activity is associated with physiological or psychological stress, which can be induced by tumor development and cancer diagnosis. Targeting the stress response through suppression of sympathetic activity or activation of parasympathetic activity has been shown to drive activation of effector T cells and inhibition of myeloid-derived suppressor cells within the tumor. In addition, there is emerging evidence that sensory nerves may regulate tumor growth and metastasis by promoting or inhibiting immunosuppression in a tumor-type specific manner. Because neural effects are often tumor-type specific, further study is required to optimize clinical therapeutic strategies. This review examines the emerging evidence that neuroimmune communication can regulate antitumor immunity as well as contribute to development of cancer-related neurological symptoms.
从进化的角度来看，神经系统和免疫细胞已经进化到可以相互交流，以控制炎症和宿主对损伤的反应。神经免疫通讯的最新发现表明，这些机制扩展到了癌症的发生和发展。淋巴结构和肿瘤通常与炎症浸润有关，它们被多种神经类型（如交感神经、副交感神经、感觉神经）高度支配。最近的临床前和临床研究表明，靶向神经系统可能是一种治疗策略，可以促进抗肿瘤免疫，同时减少与癌症相关的神经症状，如慢性疼痛、疲劳和认知障碍。交感神经活动与生理或心理压力有关，这种压力可能是由肿瘤的发展和癌症的诊断引起的。通过抑制交感神经活动或激活副交感神经活动来靶向应激反应，已被证明可以驱动效应 T 细胞的激活，并抑制肿瘤内的髓源性抑制细胞。此外，有新的证据表明，感觉神经可能通过以肿瘤类型特异性的方式促进或抑制免疫抑制来调节肿瘤的生长和转移。由于神经效应通常具有肿瘤类型特异性，因此需要进一步研究来优化临床治疗策略。这篇综述探讨了神经免疫通讯可以调节抗肿瘤免疫以及导致与癌症相关的神经症状的发展的新证据。
