Review Volume 11, Issue 23 pp 11770—11792
Cancer stem cells-driven tumor growth and immune escape: the Janus face of neurotrophins
- 1 Institute of Biochemistry and Cell Biology, National Research Council (CNR), International Campus A. Buzzati-Traverso, Monterotondo Scalo, Rome, Italy
- 2 Institute of Biochemistry and Cell Biology, National Research Council (CNR), at Department of Sense Organs, University of Rome La Sapienza, Rome, Italy
- 3 Department of Sense Organs, University of Rome La Sapienza, Rome, Italy
Received: September 12, 2019 Accepted: November 17, 2019 Published: December 7, 2019
https://doi.org/10.18632/aging.102499How to Cite
Copyright © 2019 Triaca et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Cancer Stem Cells (CSCs) are self-renewing cancer cells responsible for expansion of the malignant mass in a dynamic process shaping the tumor microenvironment. CSCs may hijack the host immune surveillance resulting in typically aggressive tumors with poor prognosis.
In this review, we focus on neurotrophic control of cellular substrates and molecular mechanisms involved in CSC-driven tumor growth as well as in host immune surveillance. Neurotrophins have been demonstrated to be key tumor promoting signaling platforms. Particularly, Nerve Growth Factor (NGF) and its specific receptor Tropomyosin related kinase A (TrkA) have been implicated in initiation and progression of many aggressive cancers. On the other hand, an active NGF pathway has been recently proven to be critical to oncogenic inflammation control and in promoting immune response against cancer, pinpointing possible pro-tumoral effects of NGF/TrkA-inhibitory therapy.
A better understanding of the molecular mechanisms involved in the control of tumor growth/immunoediting is essential to identify new predictive and prognostic intervention and to design more effective therapies. Fine and timely modulation of CSCs-driven tumor growth and of peripheral lymph nodes activation by the immune system will possibly open the way to precision medicine in neurotrophic therapy and improve patient’s prognosis in both TrkA- dependent and independent cancers.
Abbreviations
AML: Acute Myeloblastic Leukaemia; APCs: Antigen-Presenting Cells; BCL-2: B-cell lymphoma-2; BCL-XL: B-cell lymphoma-Extra Large; ICI: co-Inhibitory Immune Checkpoints; CTL: Cytotoxic T Lymphocytes; CTLA-4: Cytotoxic T-Lymphocyte Antigen-4; CTCs: Circulating Tumour Cells; CSCs: Cancer Stem Cells; DCs: Dendritic Cells; EMT: Epithelial-Mesenchymal Transition; GC: Gastric Cancer; HNSC: Head and Neck Squamous Carcinoma; MCSF: Macrophage Colony-Stimulating Factor; MDSC: Myeloid-Derived Stem Cells; MHC: Major Histocompatibility Complex; NSCLC: Non-Small Cell Lung Carcinoma; PDL1: Programmed Death-Ligand 1; PGE2: Prostaglandin E2; SCLC: Small Cell Lung Cancer; TAMs: Tumour Associated Macrophages; Tregs: Regulatory T cells; IGF: Insulin-like Growth Factor; NGF: Nerve Growth Factor; NT: Neurotrophin; VEGF: Vascular Endothelial Growth Factor; P75NTR: p75 neurotrophic receptor; TrkA: Tropomyosin related kinase A; TrkB: Tropomyosin related kinase B; TrkC: Tropomyosin related kinase C; BEX: Brain Expressed X-linked; COX-2: Cyclooxygenase-2; CREB: cAMP Response Element-Binding protein; DAMP: Danger Associated Molecular Patterns; IDO: Indoleamine 2,3-Dioxygenase; INF- γ: Interferon-γ; LINGO1: Leucine Rich Repeat And Ig Domain Containing 1; JNK: c-Jun N-terminal kinases; mTOR: mammalian Target Of Rapamicin; MAPK: Mitogen-Activated Protein Kinase; MVB: Multi-Vesicular Body; NOGO: Neurite Outgrowth inhibitor; NF- kB: Nuclear Factor- kB; NLR: Nod-like Receptor; PI3K: phosphatidylinositol 3-kinase; PLC-γ: Phospholipase C-γ; PRR: Pattern Recognition Receptor; STAT3: Signal Transducer and Activator of Transcription-3 (STAT-3); TLR: Toll Like Receptor; TEM: Tumor Micro Environment; TRADD: Tumor necrosis factor receptor type 1-associated DEATH domain-dependent; TRAL: TNF-related apoptosis-inducing ligand.