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Tumor-infiltrating CD4+ T cells in patients with gastric cancer.

ABSTRACT: T lymphocytes play an indispensably important role in clearing virus and tumor antigen. There is little knowledge about impacts of inhibitory molecules with cytokine on tumor-infiltrating CD4+ T-cells in the presence of gastric cancer (GC). This study investigated the distribution of tumor-infiltrating T-cells subset and the differentiation as well as inhibitory phenotype of T-cells from blood and tissues of GC patients.Patients with GC diagnosed on the basis of pre-operative staging and laparotomy findings were approached for enrollment between 2014 and 2015 at the Affiliated Cancer Hospital of Zhengzhou University, China. Phenotypic analysis based on isolation of tumor-infiltrating lymphocytes and intracellular IFN-? staining assay is conducted. Statistical analysis is performed to show significance.The results showed that the percentage of CD4+ T-cells among CD3+ cells in tumors was significantly higher than that in the matched paraneoplastic tissue. CD4+ CD25high CD127low regulatory T-cells (Tregs), PD-1+, Tim-3+, and PD-1+ Tim-3+ cells were up-regulated on tumor infiltrating T-cells from patients with GC compared to their expressions on corresponding peripheral blood and peritumoral T-cells. Blockades of PD-1+ and Tim-3+ were effective in restoring tumor infiltrating T-cells' production of interferon-gamma (IFN-?). Combined PD-1+ and Tim-3+ inhibition had a synergistic effect on IFN-? secretion by CD4+ T-cells.The results suggested that the composition, inhibitors, and location of the immune infiltrate should be considered when evaluating antitumor immunotherapy. A new insight into the mechanisms underlying T cell dysfunction is provided.

SUBMITTER: Yuan L

PROVIDER: S-EPMC5712164 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Tumor-infiltrating CD4<sup>+</sup> T cells in patients with gastric cancer.

Yuan Long L Xu Benling B Yuan Peng P Zhou Jinxue J Qin Peng P Han Lu L Chen Guangyu G Wang Zhenlei Z Run Zengci Z Zhao Peng P Gao Quanli Q

Cancer cell international 20171202

<h4>Background</h4>T lymphocytes play an indispensably important role in clearing virus and tumor antigen. There is little knowledge about impacts of inhibitory molecules with cytokine on tumor-infiltrating CD4<sup>+</sup> T-cells in the presence of gastric cancer (GC). This study investigated the distribution of tumor-infiltrating T-cells subset and the differentiation as well as inhibitory phenotype of T-cells from blood and tissues of GC patients.<h4>Materials and methods</h4>Patients with GC ...[more]

PMID: 29213216

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Project description:BackgroundGastric cancer (GC) is the fourth most frequently diagnosed malignancy and the second leading cause of cancer-associated mortality worldwide. The tumor microenvironment, especially tumor-infiltrating immune cells (TIICs), exhibits crucial roles both in promoting and inhibiting cancer growth. The aim of the present study was to evaluate the landscape of TIICs and develop a prognostic nomogram in GC.Materials and methodsA gene expression profile obtained from a dataset from The Cancer Genome Atlas (TCGA) was used to quantify the proportion of 22 TIICs in GC by the CIBERSORT algorithm. LASSO regression analysis and multivariate Cox regression were applied to select the best survival-related TIICs and develop an immunoscore formula. Based on the immunoscore and clinical information, a prognostic nomogram was built, and the predictive accuracy of it was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve (ROC) and the calibration plot. Furthermore, the nomogram was validated by data from the International Cancer Genome Consortium (ICGC) dataset.ResultsIn the GC samples, macrophages (25.3%), resting memory CD4 T cells (16.2%) and CD8 T cells (9.7%) were the most abundant among 22 TIICs. Seven TIICs were filtered out and used to develop an immunoscore formula. The AUC of the prognostic nomogram in the TCGA set was 0.772, similar to that in the ICGC set (0.730) and whole set (0.748), and significantly superior to that of TNM staging alone (0.591). The calibration plot demonstrated an outstanding consistency between the prediction and actual observation. Survival analysis revealed that patients with GC in the high-immunoscore group exhibited a poor clinical outcome. The result of multivariate analysis revealed that the immunoscore was an independent prognostic factor.DiscussionThe immunoscore could be used to reinforce the clinical outcome prediction ability of the TNM staging system and provide a convenient tool for risk assessment and treatment selection for patients with GC.

Dataset Information

Tumor-infiltrating CD4+ T cells in patients with gastric cancer.

Publications

Tumor-infiltrating CD4<sup>+</sup> T cells in patients with gastric cancer.

Similar Datasets

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