Cytoskeleton regulator RNA expression on cancer-associated fibroblasts is associated with prognosis and immunotherapy response in bladder cancer

Wu, Yucai; Xu, Yangyang; He, Shiming; Li, Yifan; Fan, Jie; Feng, Na; Gong, Yanqing; Li, Xuesong; Zhou, Liqun

doi:10.1016/j.heliyon.2023.e13707

Cited by 1 publication

(1 citation statement)

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“…The CYTOR lncRNA is an oncogene that is negatively associated with response, and is related to immune pathways, aberrant glycolysis, and mitochondrial respiration. CYTOR plays a role in immune cell infiltration and is positively correlated with PD-1 expression; increased expression of CYTOR correlates with worse overall survival in cancer (67)(68)(69). STMN3 is negatively correlated with response and plays an important in anergic TTT cells as well as in signal transduction, causing cellular proliferation defects and cell cycle arrest when overexpressed (70).…”

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confidence: 99%

Cellular and transcriptional profiles of peripheral blood mononuclear cells pre-vaccination predict immune response to preventative MUC1 vaccine

Yuan,

McKeague,

Raghu

et al. 2024

Preprint

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A single arm trial (NCT007773097) and a double-blind, placebo controlled randomized trial (NCT02134925) were conducted in individuals with a history of advanced colonic adenoma to test the safety and immunogenicity of the MUC1 tumor antigen vaccine and its potential to prevent new adenomas. These were the first two trials of a non-viral cancer vaccine administered in the absence of cancer. The vaccine was safe and strongly immunogenic in 43% (NCT007773097) and 25% (NCT02134925) of participants. The lack of response in a significant number of participants suggested, for the first time, that even in a premalignant setting, the immune system may have already been exposed to some level of suppression previously reported only in cancer. Single-cell RNA-sequencing (scRNA-seq) on banked pre-vaccination peripheral blood mononuclear cells (PBMCs) from 16 immune responders and 16 non-responders identified specific cell types, genes, and pathways of a productive vaccine response. Responders had a significantly higher percentage of CD4+ naive T cells pre-vaccination, but a significantly lower percentage of CD8+ T effector memory (TEM) cells and CD16+ monocytes. Differential gene expression (DGE) and transcription factor inference analysis showed a higher level of expression of T cell activation genes, such as Fos and Jun, in CD4+ naive T cells, and pathway analysis showed enriched signaling activity in responders. Furthermore, Bayesian network analysis suggested that these genes were mechanistically connected to response. Our analyses identified several immune mechanisms and candidate biomarkers to be further validated as predictors of immune responses to a preventative cancer vaccine that could facilitate selection of individuals likely to benefit from a vaccine or be used to improve vaccine responses.

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