Faculty of Medicine, The Hebrew University, Jerusalem, Israel.
Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel.
Front Immunol. 2021 Mar 22;12:617658. doi: 10.3389/fimmu.2021.617658. eCollection 2021.
T cells are essential for eradicating microorganisms and cancer and for tissue repair, have a pro-cognitive role in the brain, and limit Central Nervous System (CNS) inflammation and damage upon injury and infection. However, in aging, chronic infections, acute SARS-CoV-2 infection, cancer, chronic stress, depression and major injury/trauma, T cells are often scarce, exhausted, senescent, impaired/biased and dysfunctional. People with impaired/dysfunctional T cells are at high risk of infections, cancer, other diseases, and eventually mortality, and become multi-level burden on other people, organizations and societies. It is suggested that "Nerve-Driven Immunity" and "Personalized Adoptive Neuro-Immunotherapy" may overcome this problem. Natural Neurotransmitters and Neuropeptides: Glutamate, Dopamine, GnRH-II, CGRP, Neuropeptide Y, Somatostatin and others, bind their well-characterized receptors expressed on the cell surface of naïve/resting T cells and induce multiple direct, beneficial, and therapeutically relevant effects. These Neurotransmitters and Neuropeptides can induce/increase: gene expression, cytokine secretion, integrin-mediated adhesion, chemotactic migration, extravasation, proliferation, and killing of cancer. Moreover, we recently found that some of these Neurotransmitters and Neuropeptides also induce rapid and profound decrease of PD-1 in human T cells. By inducing these beneficial effects in naïve/resting T cells at different times after binding their receptors (. NOT by single effect/mechanism/pathway), these Neurotransmitters and Neuropeptides by themselves can activate, rejuvenate, and improve T cells. "Personalized Adaptive Neuro-Immunotherapy" is a novel method for rejuvenating and improving T cells safely and potently by Neurotransmitters and Neuropeptides, consisting of personalized diagnostic and therapeutic protocols. The patient's scarce and/or dysfunctional T cells are activated once by pre-selected Neurotransmitters and/or Neuropeptides, tested, and re-inoculated to the patient's body. Neuro-Immunotherapy can be actionable and repeated whenever needed, and allows other treatments. This adoptive Neuro-Immunotherapy calls for testing its safety and efficacy in clinical trials.
T 细胞对于消除微生物和癌症以及组织修复至关重要,在大脑中具有认知促进作用,并且在受伤和感染时限制中枢神经系统 (CNS) 的炎症和损伤。然而,在衰老、慢性感染、急性 SARS-CoV-2 感染、癌症、慢性应激、抑郁和重大损伤/创伤时,T 细胞通常会变得稀缺、耗竭、衰老、受损/偏向和功能失调。T 细胞受损/功能失调的人感染、癌症和其他疾病的风险很高,最终导致死亡率增加,并且成为其他人、组织和社会的多层次负担。有人提出“神经驱动免疫”和“个性化适应性神经免疫疗法”可能克服这个问题。天然神经递质和神经肽:谷氨酸、多巴胺、GnRH-II、CGRP、神经肽 Y、生长抑素等,与幼稚/静止 T 细胞表面表达的特征明确的受体结合,并诱导多种直接、有益且具有治疗相关性的作用。这些神经递质和神经肽可以诱导/增加:基因表达、细胞因子分泌、整合素介导的黏附、趋化性迁移、外渗、增殖和杀伤癌症。此外,我们最近发现,其中一些神经递质和神经肽也会导致人 T 细胞中 PD-1 的快速和显著下降。通过在结合受体后不同时间诱导幼稚/静止 T 细胞中的这些有益作用(. NOT 通过单一作用/机制/途径),这些神经递质和神经肽本身可以激活、恢复活力并改善 T 细胞。“个性化适应性神经免疫疗法”是一种通过神经递质和神经肽安全有效地激活和改善 T 细胞的新方法,包括个性化诊断和治疗方案。患者稀缺和/或功能失调的 T 细胞通过预先选择的神经递质和/或神经肽一次性激活、测试,并重新接种到患者体内。神经免疫疗法可以根据需要随时采取行动并重复,并且允许其他治疗。这种适应性神经免疫疗法需要在临床试验中测试其安全性和有效性。