Conversion of intratumoral regulatory T cells by human gastric cancer cells is dependent on transforming growth factor‐β1

Lu, Xiaoming; Liu, Jun; Li, Hang; Li, Wei; Wang, Xuesong; Ma, Jingwei; Tong, Qiang; Wu, Ke; Wang, Guobin

doi:10.1002/jso.22005

Cited by 26 publications

(20 citation statements)

References 36 publications

(39 reference statements)

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“…Our study confirmed that Treg density correlated with adverse prognosis, consistent with earlier studies (Kono et al , 2006; Lu et al , 2011; Tao et al , 2012a). However, FoxP3-positive tumours appear to have conflicting clinic significance.…”

Section: Discussionsupporting

confidence: 93%

“…However, FoxP3-positive tumours appear to have conflicting clinic significance. Previous studies showed that Treg counts in sentinel lymph nodes were associated with lymph node metastasis (Lee et al , 2011), where increased tumour-infiltrating Tregs positively correlated with TNM stage (Yuan et al , 2010; Liang et al , 2011; Lu et al , 2011) and the proportion of Treg/CD4 was associated with GC recurrence (Kim et al , 2011). FoxP3-positive cancer cells were associated with pathological differentiation, T stage, and poor prognosis in tongue squamous cell carcinoma (Liang et al , 2011) and lymph node metastasis in non-small cell lung cancer (Dimitrakopoulos et al , 2011).…”

Section: Discussionmentioning

confidence: 99%

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

Miao

et al. 2014

Br J Cancer

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Background:Forkhead Box P3 (FoxP3) is thought to be a key transcription factor in regulatory T cells (Tregs), and recent data indicate that it is expressed in several tumour cells. However, its precise roles in gastric cancer (GC) and the underlying mechanisms regulating the interaction between GC cells and lymphocytes remain unclear.Methods:FoxP3 expression was examined in tumour cells and Tregs in 150 cases of gastric precancer and cancer, and their prognostic significances were evaluated, respectively, using a tissue microarray containing 135 GC patient samples with a mean 102-month follow-up. FoxP3 involvement in the tumour cells–lymphocytes interaction and its gene function were further investigated.Results:strong cytoplasmic staining of FoxP3 was observed in GC cells. FoxP3 protein expression in tumour cells predicts a good prognosis, whereas high-density Treg predicts a poor prognosis. Moreover, FoxP3 expression in GC cells increased after coculture with peripheral blood mononuclear cells through coculture systems. Upregulation of FoxP3 inhibited tumour growth in tumour-bearing nude mice.Conclusions:High FoxP3 expression in tumour cells predicts better survival in GC, possibility in relation to interaction between tumour cells and lymphocytes in microenvironment. Interfering with FoxP3 expression may open a new therapeutic strategy against tumour progression.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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

Miao

et al. 2014

Br J Cancer

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“…28 Even if gastric cancer is frequently associated with Helicobacter pylori-induced gastritis, a high density of Foxp3 C cells is usually associated with a poor prognosis, as found in our present study and predominating the literature. [29][30][31][32] Only Haas et al found a relationship between high levels of Foxp3C cell tumor infiltration and improved prognosis in 52 patients bearing gastric adenocarcinomas of the cardia. 33 In the present work, we did not find a significant correlation between gastric cancer patient survival and the density of CD8 C or IL-17 C tumor-infiltrating cells.…”

Section: Discussionmentioning

confidence: 99%

Tumor infiltration by Tbet+ effector T cells and CD20+ B cells is associated with survival in gastric cancer patients

Hennequin¹,

Dérangère²,

Boidot³

et al. 2015

OncoImmunology

169

140

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These authors equally contributed to this work.yy These authors jointly supervised this work. Keywords: B cells, gastric cancer, histology, human tumors, prognosis, T-betAbbreviations: APC, antigen presenting cell; DC, dendritic cell; NK, natural killer; OS, overall survival; RFS, relapse-free survival; Th1, T helper type 1; TLS, tertiary lymphoid structures; Treg, regulatory T cell.Tumor-infiltrating T and B lymphocytes could have the potential to affect cancer prognosis. The objective of this study was to investigate the prognostic significance of tumor infiltration by CD8 and CD4 T cells, and B lymphocytes in patients with localized gastric cancer. In a retrospective cohort of 82 patients with localized gastric cancer and treated by surgery we quantitatively assessed by immunohistochemistry on surgical specimen, immune infiltrates of IL-17 C , CD8 C , Foxp3 C , Tbet C T cells and CD20 C B cells both in the tumor core and at the invasive margin via immunohistochemical analyses of surgical specimens. We observed that CD8 C and IL17 C T-cell densities were not significantly associated with gastric cancer prognosis. In contrast, high infiltration of Tbet C T cells, high numbers of CD20 C B-cell follicles, and low infiltration of Foxp3 C T cells, were associated with better relapse-free survival. Interestingly, treatment with neoadjuvant chemotherapy or histological tumor type (diffuse versus intestinal) did not influence type and density of immune infiltrates or their prognostic value. Immunohistochemical analysis of the gastric cancer stromal microenvironment revealed organized T and B cell aggregates, with strong structural analogies to normal secondary lymphoid organs and which could be considered as tertiary lymphoid structures. Using transcriptomic data from an independent cohort of 365 localized gastric cancer, we confirmed that a coordinated Th1, and B cell stromal gene signature is associated with better outcome. Altogether, these data suggest that tumor infiltration by B and Th1 T cells could affect gastric cancer prognosis and may be used to better define the outcome of patients with localized gastric cancer.

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“…It acts as a suppressor for tumor formation in normal intestinal epithelium while a promoter for tumor invasion, metastasis and tumor stem cell maintenance after cancer occurrence (Inman, 2011;Teicher, 2001). TGF-β1-509 C>T polymorphism may regulate gene expression, and are subsequently presumed to be correlated with risk of gastric cancer formation (Lu et al, 2011;Perera et al, 2010). Although many epidemiological studies regarding TGF-β1-509 C>T polymorphism on the risk of DTC have been conducted, the results varied and were conflicting because of various reasons, such as different participants' ethnicities and resident areas, sample size, environmental factors and diet habits.…”

Section: Discussionmentioning

confidence: 99%

Correlation between TGF-β1-509 C>T polymorphism and risk of digestive tract cancer in a meta-analysis for 21,196 participants

Zhang

Cui

Xia³

et al. 2012

Gene

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Conversion of intratumoral regulatory T cells by human gastric cancer cells is dependent on transforming growth factor‐β1

Abstract: The proportion of functional Treg is elevated in human gastric cancer and related to poor prognosis. Gastric cancer cells directly convert CD4(+) naive T cells to Treg by TGF-β1, suggesting a possible mechanism through which tumor cells evade the immune system.

Cited by 26 publications

References 36 publications

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

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

Tumor infiltration by Tbet+ effector T cells and CD20+ B cells is associated with survival in gastric cancer patients

Correlation between TGF-β1-509 C>T polymorphism and risk of digestive tract cancer in a meta-analysis for 21,196 participants

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