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Possible Mechanisms Responsible for Stress Predisposition to Cancer or to Autoimmune Diseases

Paolo Lissoni*, Giusy Messina, Roberto Trampetti, Andrea Sassola, Enrica Porta, Giorgio Porro and Giuseppe Di Fede

Institute of Biological Medicine, Milan, Italy.

ABSTRACT

Today it is known that the enhanced brain opioid system activity represent the major neurochemical variation occurring in stress conditions. Moreover, it has been shown that a chronic opioid hyperactivation may suppress the anticancer immunity, and promote cancer development. On the contrary, the influence of stress on the autoimmune processes is more complex, since the mu-opioid agonists may stimulate both TGF-beta and IL-17 secretion, which respectively may counteract or promote the onset of the autoimmune diseases. The in vivo preferential effects of opioids on TGF- beta or IL-17 secretions could depend on the functional status of brain cannabinoid system, which has been found to inhibit IL-17 secretion. Then, the neurochemical corrections of the major stress-related neuroendocrine and cytokine alterations could constitute a new physiological approach in the treatment of stress-related disorders.

INTRODUCTION 

It is known that stress may predispose to both cancer and autoimmune diseases [1-3]. Then, the physiopathological question is to establish whether the promoting influence of stress on the development both cancer and autoimmune diseases, which are characterized by the opposite immune reactivity, may depend on the type of stress or on the different immunobiological response. Moreover, despite the complexity of its mechanisms, it has been proven that stress is mainly characterized by en enhanced brain opioid system activity, since it has been demonstrated that the concomitant administration of an opioid antagonist, such as naloxone o naltrexone (NTX), may abrogate stress-induced immune alterations [4]. Moreover, stress has appeared to be characterized by an enhanced secretion of vasopressin, the so called Antidiuretic Hormone (ADH), by the neurohypophysis, as well as by an increased CRH production at hypothalamic level, with a following activation of the Hypothalamic-Pituitary- Adrenal (HPA) axis and the sympathetic system [5,6]. The mu-opioid agonists, such as beta-endorphin and morphine, have been proven to induce immunosuppression by inhibiting TH1 lymphocyte and dendritic cell functions and by stimulating regulatory T lymphocyte (T reg) system [7,8], with a consequent decreased secretion of IL-2 and IL- 12 in association with an enhanced production of TGF-beta . Being IL-2 and IL-12 the main antitumor cytokines in humans [9,10], and TGF-beta the main endogenous

*Corresponding Author: Paolo Lissoni, Institute of Biological Medicine, Milan, Italy,

Published Date: 07-2020

Copyright© 2020 Paolo Lissoni et al., Journal Of Clinical Neurology, Neurosurgery And Spine. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Citation for this article: Paolo Lissoni, Giusy Messina, Roberto Trampetti, Andrea Sassola, Enrica Porta, Giorgio Porro and Giuseppe Di Fede. Possible Mechanisms Responsible for Stress Predisposition to Cancer or to Autoimmune Diseases. Journal Of Clinical Neurology, Neurosurgery And Spine. 2020; 3(1):124

Possible Mechanisms Responsible for Stress Predisposition to Cancer or to Autoimmune Diseases

Riferimenti: Cannabinoid system, Melatonin, Neuroimmunomodulation, Opioid system, Pineal gland, Stress


Modulazione degli effetti immunitari e antitumorali dell’immunoterapia del cancro con anticorpi monoclonali Anti-Pd-1 da parte dell’ormone melatonina: Risultati Clinici Preliminari

Modulation of Immune and Anti-Tumor Effects of Cancer Immunotherapy with Anti-Pd-1 Monoclonal Antibodies by the Pineal Hormone Melatonin: Preliminary Clinical Results


Paolo Lissoni, Giusy Messina, Gianmaria Borsotti, Alessio Tosatto, Stefano Frigerio, Simonetta Tassoni* and Giuseppe Di Fede

Effata Institute of Biological Medicine, Milan, Italy.

La recente immunoterapia contro il cancro che sfrutta gli inibitori dell’espressione del PD-1 e dei suoi ligandi rappresenta una delle strategie più promettenti nella cura del cancro. Quindi, la domanda principale è come rendere la sua efficacia terapeutica massima, e questa potrebbe potenzialmente essere raggiunta dalla sua associazione con la chemioterapia, l’immunoterapia dell’Il-2 e le strategie anti-angiogeniche. Considerando che il sistema immunitario è fisiologicamente regolato da una regolazione neuroendocrina, un’altra possibile strategia per migliorare l’efficacia dell’immunoterapia oncologica potrebbe consistere in un approccio neuro immune, in particolare usando l’ormone pineale melatonina (MLT), che attualmente è la molecola neuroendocrina endogena fornita di proprietà antitumorali e immunostimolanti più studiata. Su queste basi è stato pianificato uno studio per valutare gli effetti di una somministrazione di MLT ad alte dosi in pazienti con carcinoma metastatico trattati con anticorpo monoclonale anti-PD-1 Nivolumab (NIVO). Lo studio ha incluso 14 pazienti e i risultati sono stati confrontati con quelli osservati in un gruppo di controllo di 50 pazienti. Carcinoma polmonare a piccole cellule e melanoma erano i tipi di tumore più frequenti. La MLT è stata somministrata per via orale a 100 mg / die durante il periodo buio della giornata e NIVO è stato iniettato a dosi di 3 mg / kg di peso corporeo, a intervalli di 15 giorni. La percentuale di regressioni tumorali di controllo della malattia (DC) era più alta nei pazienti trattati contemporaneamente con MLT, anche se l’unica differenza nella DC era statisticamente significativa. Questa evidenza è stata associata ad un aumento significativamente più elevato del rapporto linfociti-monociti (LMR) nel gruppo MLT, suggerendo che la MLT può essere associata con successo agli anticorpi monoclonali anti-PD-1 per pilotare la risposta immunitaria in modo antitumorale, stimolando proliferazione dei linfociti e inibizione dello stato infiammatorio indotto dai macrofagi, che sopprime l’immunità antitumorale.

*Corresponding Author: Simonetta Tassoni, Effata Institute of Biological Medicine, Lucca, Italy.

Published Date: 02-08-2020

Copyright© 2020 by Lissoni P, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

https://maplespub.com/article/Modulation-of-Immune-and-Anti-Tumor-Effects-of-Cancer-Immunotherapy-with-Anti-Pd-1-Monoclonal-Antibodies-by-the-Pineal-Hormone-Melatonin-Preliminary-Clinical-Results

 

Riferimenti: Anti-PD-1 Monoclonal Antibodies, Cancer Immunotherapy, Checkpoint Inhibitors, Melatonin, Neuroimmune Modulation

Copyright by IMBIO 2017. All rights reserved.