Transcriptional neural-like signaling contributes to an immune-suppressive tumor microenvironment.

Autor: Dai H; Cygnal Therapeutics Cambridge Massachusetts USA., Lou S; Cygnal Therapeutics Cambridge Massachusetts USA., Zhang Y; Cygnal Therapeutics Cambridge Massachusetts USA., Thanawala M; Cygnal Therapeutics Cambridge Massachusetts USA., Huang KC; Cygnal Therapeutics Cambridge Massachusetts USA., Ji L; Cygnal Therapeutics Cambridge Massachusetts USA., Carden S; Cygnal Therapeutics Cambridge Massachusetts USA., Liao T; Cygnal Therapeutics Cambridge Massachusetts USA., Abbassi M; Cygnal Therapeutics Cambridge Massachusetts USA., Shu CJ; Cygnal Therapeutics Cambridge Massachusetts USA., Lantermann A; Cygnal Therapeutics Cambridge Massachusetts USA., Sadaghiani M; Cygnal Therapeutics Cambridge Massachusetts USA., Blom D; Cygnal Therapeutics Cambridge Massachusetts USA., Wagner J; Cygnal Therapeutics Cambridge Massachusetts USA., Huang P; Cygnal Therapeutics Cambridge Massachusetts USA.
Jazyk: angličtina
Zdroj: FASEB bioAdvances [FASEB Bioadv] 2021 Oct 04; Vol. 4 (1), pp. 76-89. Date of Electronic Publication: 2021 Oct 04 (Print Publication: 2022).
DOI: 10.1096/fba.2021-00076
Abstrakt: 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.
(© 2021 Cygnal Therapeutics. FASEB BioAdvances published by Wiley Periodicals LLC on behalf of The Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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