High FoxP3 expression in tumour cells predicts better survival in gastric cancer and its role in tumour microenvironment

Gf, Ma; Miao, Qing; Ym, Liu; Gao, Huile; Jj, Lian; Yn, Wang; Xq, Zeng; Tc, Luo; Ll, Ma; Shen, Zhiqiang; Sun, Ying; Sy, Chen

doi:10.1038/bjc.2014.47

Cited by 71 publications

(57 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We previously showed that gastric cancer cells express IL-10 and that serum IL-10 concentrations tend to be higher in gastric cancer patients than in normal controls [39,40]. Furthermore, the number of Treg cells, the main source of IL-10, was found to be increased in blood and tumor tissue of gastric cancer patients [41]. We therefore postulate that the increase we observed in IgG4-positive cells in gastric cancer tissue is associated with IL-10 expression.…”

Section: Discussionsupporting

confidence: 51%

A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis

et al. 2016

View full text Add to dashboard Cite

IgG4-related disease is a newly defined disease characterized by elevated serum IgG4 levels and infiltration of affected organs by IgG4-positive plasma cells. Recently, increased IgG4 levels were reported to be closely related with malignancy. To assess the relationship between IgG4 and the progression of gastric cancer, we immunohistochemically stained in this study gastric cancer tissue samples for IgG4-positive cells using an anti-IgG4 antibody. In addition, pre- and postoperative serum concentrations of IgG4 were measured, using an enzyme-linked immunosorbent assay. In gastric cancer samples, the number of CD138-positive plasma cells was significantly lower and the number of IgG4-positive cells significantly higher than in non-cancerous gastric mucosa. The number of IgG4-positive cells was significantly correlated with gross tumor appearance, tumor depth, lymph node metastasis, venous invasion, and lymphatic invasion. Prognosis was significantly poorer in patients with a high number of IgG4-positive cells than in those with a low number. Multivariate analysis indicated that both the number of IgG4-positive cells and the depth of tumor invasion were independently prognostic of survival. In conclusion, in gastric cancer, the number of IgG4-positive cells is increased and this is closely associated with gastric cancer progression.

show abstract

Section: Discussionsupporting

confidence: 51%

A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…This result, which is based on the expression of our 32-gene signature, is also in line with previous clinical findings pertaining to the CD8+ T cell to Treg ratio in the tumor microenvironment [38,44]. Furthermore, we observed that FOXP3 expression was significantly elevated in the clinically favorable cluster of patient tumor samples (cluster1, P < 5.41e-14; data not shown), which is also in accord with previous FOXP3 related studies [45][46][47][48][49].…”

Section: Discussionsupporting

confidence: 93%

Identification of an immune gene expression signature associated with favorable clinical features in Treg-enriched patient tumor samples

Givechian¹,

Wnuk²,

Garner³

et al. 2018

Preprint

View full text Add to dashboard Cite

Identification of an immune gene expression signature associated with favorable clinical features in Treg-enriched patient tumor samples AbstractImmune heterogeneity within the tumor microenvironment undoubtedly adds several layers of complexity to our understanding of drug sensitivity and patient prognosis across various cancer types. Within the tumor microenvironment, immunogenicity is a favorable clinical feature in part driven by the antitumor activity of CD8+ T cells. However, tumors often inhibit this antitumor activity by exploiting the suppressive function of Regulatory T cells (Tregs), thus suppressing the adaptive immune response. Despite the seemingly intuitive immunosuppressive biology of Tregs, prognostic studies have produced contradictory results regarding the relationship between Treg enrichment and survival. We therefore analyzed RNA-seq data of Treg-enriched tumor samples to derive a pan-cancer gene signature able to help reconcile the inconsistent results of Treg studies, by better understanding the variable clinical association of Tregs across alternative tumor contexts. We show that increased expression of a 32-gene signature in Treg-enriched tumor samples (n=135) is able to distinguish a cohort of patients associated with chemosensitivity and overall survival This cohort is also enriched for CD8+ T cell abundance, as well as the antitumor M1 macrophage subtype. With a subsequent validation in a larger TCGA pool of Treg-enriched patients (n = 626), our results reveal a gene signature able to produce unsupervised clusters of Treg-enriched patients, with one cluster of patients uniquely representative of an immunogenic tumor microenvironment. Ultimately, these results support the proposed gene signature as a putative biomarker to identify certain Treg-enriched patients with immunogenic tumors that are more likely to be associated with features of favorable clinical outcome.

show abstract

“…Through enumeration of CD8 + T cells of the IM, we found that the CD8 + T cell number on the tumor side had a greater effect on OS than that on the stromal side (P = 0.01, Figure 3, A and B + OSCC, and gastric cancer (34,35). Based on a positive correlation between an increased number of Tregs and the CD8 + T cell infiltrate (Figure 4), we posited that Tregs recruited to the TME might not be close enough to the CD8 + T cells to suppress their effector function.…”

Section: Density Of Cd8mentioning

confidence: 96%

Multiparametric immune profiling in HPV– oral squamous cell cancer

et al. 2017

View full text Add to dashboard Cite

High FoxP3 expression in tumour cells predicts better survival in gastric cancer and its role in tumour microenvironment

Cited by 71 publications

References 38 publications

A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis

A high number of IgG4-positive cells in gastric cancer tissue is associated with tumor progression and poor prognosis

Identification of an immune gene expression signature associated with favorable clinical features in Treg-enriched patient tumor samples

Multiparametric immune profiling in HPV– oral squamous cell cancer

Contact Info

Product

Resources

About