Mardelle Ugo, Bretaud Ninon, Daher Clara, Feuillet Vincent
Aix-Marseille Université, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), CIML, Centre d'Immunologie de Marseille-Luminy, Marseille, France.
Front Immunol. 2024 Feb 16;15:1335387. doi: 10.3389/fimmu.2024.1335387. eCollection 2024.
The nervous and immune systems are the primary sensory interfaces of the body, allowing it to recognize, process, and respond to various stimuli from both the external and internal environment. These systems work in concert through various mechanisms of neuro-immune crosstalk to detect threats, provide defense against pathogens, and maintain or restore homeostasis, but can also contribute to the development of diseases. Among peripheral sensory neurons (PSNs), nociceptive PSNs are of particular interest. They possess a remarkable capability to detect noxious stimuli in the periphery and transmit this information to the brain, resulting in the perception of pain and the activation of adaptive responses. Pain is an early symptom of cancer, often leading to its diagnosis, but it is also a major source of distress for patients as the disease progresses. In this review, we aim to provide an overview of the mechanisms within tumors that are likely to induce cancer pain, exploring a range of factors from etiological elements to cellular and molecular mediators. In addition to transmitting sensory information to the central nervous system, PSNs are also capable, when activated, to produce and release neuropeptides (e.g., CGRP and SP) from their peripheral terminals. These neuropeptides have been shown to modulate immunity in cases of inflammation, infection, and cancer. PSNs, often found within solid tumors, are likely to play a significant role in the tumor microenvironment, potentially influencing both tumor growth and anti-tumor immune responses. In this review, we discuss the current state of knowledge about the degree of sensory innervation in tumors. We also seek to understand whether and how PSNs may influence the tumor growth and associated anti-tumor immunity in different mouse models of cancer. Finally, we discuss the extent to which the tumor is able to influence the development and functions of the PSNs that innervate it.
神经和免疫系统是人体主要的感觉界面，使人体能够识别、处理并对来自外部和内部环境的各种刺激做出反应。这些系统通过神经 - 免疫相互作用的各种机制协同工作，以检测威胁、抵御病原体并维持或恢复体内平衡，但也可能导致疾病的发生。在外周感觉神经元（PSN）中，伤害性PSN尤其受到关注。它们具有在外周检测有害刺激并将此信息传递至大脑的显著能力，从而导致疼痛感知和适应性反应的激活。疼痛是癌症的早期症状，常常促使其得以诊断，但随着疾病进展，它也是患者痛苦的主要来源。在本综述中，我们旨在概述肿瘤内可能诱发癌痛的机制，探讨从病因要素到细胞及分子介质等一系列因素。除了将感觉信息传递至中枢神经系统外，PSN在激活时还能够从其外周终末产生并释放神经肽（例如降钙素基因相关肽和P物质）。这些神经肽已被证明在炎症、感染和癌症情况下可调节免疫。PSN常常存在于实体瘤内，很可能在肿瘤微环境中发挥重要作用，潜在地影响肿瘤生长和抗肿瘤免疫反应。在本综述中，我们讨论了关于肿瘤中感觉神经支配程度的现有知识状态。我们还试图了解在不同的癌症小鼠模型中，PSN是否以及如何影响肿瘤生长和相关的抗肿瘤免疫。最后，我们讨论肿瘤能够在多大程度上影响支配它的PSN的发育和功能。
