The Role of Nerve Fibers in the Tumor Immune Microenvironment of Solid Tumors

• Published in: Advanced biology 2022-09, Vol.6 (9), p.e2200046-n/a
• Main Authors: Hernandez, Sharia, Serrano, Alejandra G., Solis Soto, Luisa M.
• Format: Article
• Language: English
• Subjects: cancer; Humans; Immunohistochemistry; Neoplasms - metabolism; nerve density; Nerve Fibers - pathology; Neurons - metabolism; perineural niche; tumor microenvironment; Tumor Microenvironment - physiology; tumor‐associated nerves
• ISSN: 2701-0198; 2701-0198
• DOI: 10.1002/adbi.202200046

The importance of neurons and nerve fibers in the tumor microenvironment (TME) of solid tumors is now acknowledged after being unexplored for a long time; this is possible due to the development of new technologies that allow in situ characterization of the TME. Recent studies have shown that the density and types of nerves that innervate tumors can predict a patient's clinical outcome and drive several processes of tumor biology. Nowadays, several efforts in cancer research and neuroscience are taking place to elucidate the mechanisms that drive tumor‐associated innervation and nerve‐tumor and nerve‐immune interaction. Assessment of neurons and nerves within the context of the TME can be performed in situ, in tumor tissue, using several pathology‐based strategies that utilize histochemical and immunohistochemistry principles, hi‐plex technologies, and computational pathology approaches to identify measurable histopathological characteristics of nerves. These features include the number and type of tumor associated nerves, topographical location and microenvironment of neural invasion of malignant cells, and investigation of neuro‐related biomarker expression in nerves, tumor cells, and cells of the TME. A deeper understanding of these complex interactions and the impact of nerves in tumor biology will guide the design of better strategies for targeted therapy in clinical trials. Recent studies have found that the interaction of the nervous system with tumor cells, immune cells, and other elements of the tumor microenvironment are implicated in tumor biology, and its understanding is important to developing novel cancer treatments. Assessment of nerves in situ in tumor tissue using tissue‐based techniques offers opportunities to advance our knowledge in this exciting research area.