Transcriptional neural‐like signaling contributes to an immune‐suppressive tumor microenvironment

Autor: Hongyue Dai, Shan Lou, Yanbo Zhang, Monica Thanawala, Kai‐Chih Huang, Lexiang Ji, Sarah Carden, Tiffany Liao, Mandana Abbassi, Chengyi J. Shu, Alexandra Lantermann, Masoud Sadaghiani, Daniel Blom, John Wagner, Pearl Huang
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: FASEB BioAdvances, Vol 4, Iss 1, Pp 76-89 (2022)
Druh dokumentu: article
ISSN: 2573-9832
DOI: 10.1096/fba.2021-00076
Popis: Abstract Tumor innervation has recently been documented and characterized in various settings and tumor types. However, the role that nerves innervating tumors play in the pathogenesis of cancer has not been clarified. In this study, we searched for neural signaling from bulk RNA sequencing from The Cancer Genome Atlas (TCGA) dataset and looked for patterns of interactions between different cell types within the tumor environment. Using a presynapse signature (PSS) as a probe, we showed that multiple stromal cell types crosstalk and/or contribute to neural signals. Based on the correlation and linear regression, we hypothesized that neural signals contribute to an immune‐suppressive tumor microenvironment (TME). To test this hypothesis, we performed in vitro dorsal root ganglion (DRG)/macrophage coculture experiments. Compared to the M2 macrophage monoculture, the DRG/M2 macrophage coculture prevented anti‐inflammatory M2 to pro‐inflammatory M1 polarization by LPS stimulation. Finally, a survey of different TCGA tumor types indicated that higher RNA neural signature is predictive of poor patient outcomes in multiple tumor types.
Databáze: Directory of Open Access Journals