The Neuroimmune Axis in the Tumor Microenvironment

Abstract

Cancer is a complex ecosystem and should be considered in the context of its cellular and molecular microenvironment, which includes the nerves. Peripheral nerves can modulate phenotype and behavior of the malignant cells and thus affect tumor growth and metastasis. Only recently has the role of neuroimmune cross-talk surfaced as a key contributor to cancer progression. However, little is known about the immunomodulatory role of the neuroglial cells in cancer progression and metastasis and the response to therapy. Schwann cells, the principal glial cells of the peripheral nervous system, are now considered to be important players in the tumor microenvironment. They can directly accelerate malignant cell migration and the formation of metastases. Better understanding of the neuroimmune circuits in the tumor milieu will be instrumental in the development of novel therapeutic approaches for the malignancies known to be associated with inflammation and dysregulated immune responses.

Long Non-Coding RNAs in the Tumor Immune Microenvironment: Biological Properties and Therapeutic Potential

“…The TME is a complex and dynamic network structure composed of tumor cells and the surrounding region (including tumor-associated immune cells, fibroblasts, vascular endothelial cells, adipocytes and extracellular matrix, as well as secreted cytokines and chemokines) (5). The immune microenvironment, hypoxic niche, metabolism microenvironment, acidic niche and innervated niche microenvironment, and other microenvironments are interconnected, which significantly contributes to the complexity and heterogeneity of the TME (6)(7)(8)(9)(10)(11)(12). The immune microenvironment is considered to be a critical specialized microenvironment that can reprogram cancer biology, and is closely related to cancer prognosis and response to treatment (7,13).…”

The updated landscape of tumor microenvironment and drug repurposing

“…The innervation of cancer cells or stromal cells always relies on the release of neurotransmitters or neuropeptides, such as dopamine, catecholamine, and acetylcholine. 27 The axonal microenvironment promotes the formation and development of schwannoma, a benign nerve sheath neoplasm. 116 , 117 Gastric cancer secretes neurotrophins to promote nerve infiltration in TME.…”

“… 28 Released catecholamine may promote lymphocyte apoptosis and macrophage infiltration, inhibit NK cells and cytotoxic T cells, and thus facilitate tumor metastasis. 27 , 145 , 146 High levels of norepinephrine suppress DC development and recruit MDSC to TME, causing tumor progression. 147 The sympathetic nervous system guides the recruitment of macrophages or NK cells to tumor via β-adrenergic signaling.…”

The Interplay between Housing Environmental Attributes and Design Exposures and Psychoneuroimmunology Profile—An Exploratory Review and Analysis Paper in the Cancer Survivors’ Mental Health Morbidity Context

“…Inflammatory systemic response-derived factors involve tissue-specific immunity [225] and the release of pro-inflammatory mediators by many tissues [226,227]. A complex set of interactions between inflammatory mediatorsvasoactive amines and peptides, complement components, lipid mediators, cytokines, chemokines, proteolytic enzymes [228], transcription and growth factors [229], acutephase proteins [230]-and effector cells-myeloid and lymphoid [231,232], epithelial [233], endothelial [234], stromal [235] cells-as well as their receptors [236], could operate in different step-wise sequences overlapped in chronological terms in getting a pathological neuroimmunological environment to cancer progression [237,238], behavioural symptoms [239] and psychiatric disorders [240].…”