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Review
. 2021 Oct;99(9):949-961.
doi: 10.1111/imcb.12496. Epub 2021 Sep 12.

Neuroimmunology of cancer and associated symptomology

Nicole N Scheff  1 , Jami L Saloman  1
Affiliations
Review

Neuroimmunology of cancer and associated symptomology

Nicole N Scheff et al. Immunol Cell Biol. 2021 Oct.

Abstract

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.

Keywords: metastasis; peripheral nerves; proliferation; tumor immunity.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors have no conflicts of interest to report.

Figures

Figure 1.
Figure 1.
The cancer–neuroimmune network. The tumor microenvironment contains malignant cells, subsets of effector and regulatory immune cells and the peripheral nervous system composed of three different populations of peripheral nerves (e.g. sympathetic, parasympathetic and sensory). The representative schematic of communication between the peripheral nervous system and tumor-associated immune cells including myeloid-derived cells [i.e. myeloid-derived suppressor cell (MDSC), macrophage, monocyte, neutrophil] and lymphocytes [i.e. natural killer (NK) cell, CD8+ T cell] is based on recent findings. Selective manipulation of neurotransmission alters the number and/or activity of the indicated immune target in the direction indicated by the arrow. Cell communication can be either direct or mediated by cytokines, chemokines, growth factors and checkpoint proteins [i.e. tumor necrosis factor alpha (TNF-α), programmed cell death-1 (PD1)]. Intratumoral neurotransmitters and neuropeptides are known to regulate cancer progression by their direct effects on malignant cells and the modulation of tumor-infiltrating immune cell function. Activation/blockade of neurotransmission elicits protumor and antitumor immune responses in a nerve-type and tumor-type-dependent manner.
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References

    1. Mignini F, Streccioni V, Amenta F. Autonomic innervation of immune organs and neuroimmune modulation. Auton Autacoid Pharmacol 2003; 23: 1–25. - PubMed
    1. Coutu DL, Kokkaliaris KD, Kunz L, Schroeder T. Three-dimensional map of nonhematopoietic bone and bone-marrow cells and molecules. Nat Biotechnol 2017; 35: 1202–1210. - PubMed
    1. Hu D, Al-Shalan HAM, Shi Z, et al. Distribution of nerve fibers and nerve-immune cell association in mouse spleen revealed by immunofluorescent staining. Sci Rep 2020; 10: 9850. - PMC - PubMed
    1. Dantzer R Neuroimmune interactions: from the brain to the immune system and vice versa. Physiol Rev 2018; 98: 477–504. - PMC - PubMed
    1. Reavis HD, Chen HI, Drapkin R. Tumor innervation: cancer has some nerve. Trends Cancer 2020; 6: 1059–1067. - PMC - PubMed

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