Prognostic significance of PD‐L1 expression on cell‐surface vimentin‐positive circulating tumor cells in gastric cancer patients

Abstract

Although circulating tumor cells (CTCs) have shown promise as potential biomarkers for diagnostic and prognostic assessment in gastric cancer (GC), determining the predictive and prognostic value of programmed death‐ligand 1 (PD‐L1)‐positive CTCs in patients with GC is a challenge. Here, we identified that the expression of total vimentin (VIM) protein was positively correlated with PD‐L1 and inhibited CD8+ T‐cell activation in patients with GC according to bioinformatics analysis. Notably, coexpression of PD‐L1 and cell‐surface VIM (CSV) was detected by immunofluorescence and immunohistochemistry assay in locally advanced GC tumor specimens and metastatic lymph nodes. Likewise, CSV expression level was significantly decreased after transiently knocking down PD‐L1 in GC cell lines. Based on our established CTC detection platform, CTCs were isolated from peripheral blood samples collected from 70 patients (38 resectable and 32 unresectable) with GC using magnetic positive selection and a CSV‐specific monoclonal antibody, 84‐1. CSV+PD‐L1+CTCs were observed in 50 of 70 (71%) GC patient samples, ranging from 0 to 261 mL−1. A higher number of CSV+PD‐L1+CTCs were significantly associated with a short survival duration and poor therapeutic response. This study demonstrated that detection of PD‐L1+CTCs using a CSV‐enrichment method has promising value as a clinically relevant prognostic marker for GC.

Mechanical and Non‐Mechanical Functions of Filamentous and Non‐Filamentous Vimentin

“…[87] Secretion by both macrophages and endothelial cells requires post-translational modification of vimentin, and antibodies specific to cell surface vimentin can be generated. [88,89] An important finding is that cell surface vimentin appears to be mainly in the form of oligomers with 4-12 monomers, but is not filamentous, a difference that is likely to relate to the much higher affinity of the oligomers to lipid bilayers compared with VIFs. [90] Other mechanisms by which extracellular vimentin can be generated are illustrated in some of the examples listed below and summarized in Table 1.…”

“…[88,98] Gastric cancer cells also express cell surface vimentin, and a magnetic bead isolation assay identified circulating tumor cells (CTCs) in peripheral blood of the majority of gastric cancer patients, with high vimentin positive CTCs correlating with poor prognosis. [89] Surface vimentin positive CTCs also have potential as predictors of relapse in postremission neuroblastoma. [99] Three different human prostate cell lines express vimentin that can be detected by monoclonal antibodies recognizing the coil one rod domain and the C-terminus of vimentin.…”

“…A number of approaches have used antibodies to extracellular vimentin in conjunction with antibodies to other cell surface markers to detect and isolate circulating cancer cells. [89,102,103,136] Both monoclonal anti-vimentin and a vimentinspecific DNA aptamer are being used to isolate circulating cancer cells or block the effect of vimentin. [137] Similar approaches are being applied to infection by SARS-CoV, [120] SARS2-CoV, [138] and other viruses.…”

A Predictive Nomogram for Early Death of Metastatic Gastric Cancer: A Retrospective Study in the SEER Database and China

“…However, one-third and one-fifth of early death which was defined as death came up within 3 months occurred in the SEER cohort and the Chinese cohort of this study, respectively. Researchers concentrated deeply on associated independent variables of overall survival, cancer-specific survival, and noncancer-specific survival in gastric cancer [17][18][19]. And nomograms had been widely developed and used for predicting long-term survival of cancers [20][21][22][23][24].…”

The Higher Sensitivity of GABAergic Compared to Glutamatergic Neurons to Growth-Promoting C3bot Treatment Is Mediated by Vimentin

“…Vimentin, besides its role in the formation of the intracellular intermediate filament system, has gained recent attention as a surface-expressed protein, providing a docking structure for invading pathogens in a variety of cell types, amongst them the SARS-associated coronavirus (Mak and Brüggemann, 2016 ; Yu et al, 2016 ). Also, this surface expression has been linked to malignant tumor progression (Liu et al, 2020 ). Various posttranslational modifications such as citrullination or phosphorylation are involved in the regulation of vimentin secretion into the extracellular fluid or in mediating surface presentation in different cell types (for review see Patteson et al, 2020 ).…”