Abstract
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 (i.e. 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 ex vivo 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.
Highlights
We found all the following significant findings: 1. The Hepatocellular carcinoma (HCC) patients had 5–10 fold less T cells than healthy subjects, 2
In our most recent study we studied the direct effects of Dopamine, Glutamate, GnRH-II, CGRP or Neuropeptide Y (Figure 2B) on CD3+ peripheral T cells of few elderly people aged 79–86 years, suffering from HCC and a kaleidoscope of comorbid conditions
My opinion and vision is that the direct communication between the nervous system and T cells and other immune cells, via Neurotransmitters and Neuropeptides, is essential and beneficial for all involved sides, and can be translated into therapeutic terms (Figure 2D)
Summary
Reviewed by: Elena Gonzalez-Rey, Instituto de Parasitologıa y Biomedicina Lopez-Neyra (IPBLN), Spain Elena Zenaro, University of Verona, Italy. In contrast to T cells of healthy subjects (Figure 1Aleft side), the T cells of numerous people in various abnormal conditions (Figure 1A-right) are scarce and/or exhausted, senescent, impaired, biased, and often suffer from altered stemness and do not function properly This is the case for elderly people [4,5,6,7,8,9,10], and for patients with either: chronic infections [11,12,13,14,15,16,17,18,19,20], acute SARS-Cov-2 infection and the resulting Covid-19 disease [21,22,23,24,25,26,27], cancer [2,3,4,5], chronic-stress [28,29,30,31,32,33], major depression [6, 7], sleep abnormalities [7, 8], and major injury/trauma [2, 3]. The similarities between T cells of elderly people and senescent cells include shorter telomers, accumulated DNA damage, and metabolic changes [16, 17]
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