CCR7 Expression and Intratumoral FOXP3+ Regulatory T Cells are Correlated with Overall Survival and Lymph Node Metastasis in Gastric Cancer

Zhou, Shuang; Xu, Shuchang; Tao, Huihong; Zhen, Zhiwei; Chen, L.; Zhang, Zhiqiang; Yang, Yaoqin

doi:10.1371/journal.pone.0074430

Cited by 44 publications

(45 citation statements)

References 38 publications

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“…A negative prognostic impact of tumor-infiltrating regulatory T cells has been shown for several types of cancer, including gastric cancer. [46][47][48][49][50][51][52][53] The comprehensive mutational analysis in this study is in concordance with the findings of other studies. 54 That we could not find a correlation between the genomic profile and expression of immune checkpoint receptors is probably due to the low frequencies of the analyzed mutations.…”

Section: Cd25supporting

confidence: 92%

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

et al. 2015

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Remarkable efficacy of immune checkpoint inhibition has been reported for several types of solid tumors and early studies in gastric adenocarcinoma are promising. A detailed knowledge about the natural biology of immune checkpoints in gastric adenocarcinoma is essential for clinical and translational evaluation of these drugs. This study is a comprehensive analysis of cytotoxic T lymphocyte associated molecule 4 (CTLA-4) and programmed death 1 ligand 1 (PD-L1) expression in gastric adenocarcinoma. PD-L1 and CTLA-4 were stained on tumor sections of 127 Caucasian patients with gastric adenocarcinoma by immunohistochemistry (IHC) and somatic mutation profiling was performed using targeted nextgeneration sequencing. Expression of PD-L1 and CTLA-4 on lymphocytes in tumor sections, tumordraining lymph nodes (TDLN) and peripheral blood were studied by flow-cytometry and immune-fluorescence microscopy in an additional cohort. PD-L1 and CTLA-4 were expressed in 44.9% (57/ 127) and 86.6% (110/127) of the analyzed gastric adenocarcinoma samples, respectively. Positive tumor cell staining for PD-L1 or CTLA-4 was associated with inferior overall survival. Somatic mutational analysis did not reveal a correlation to expression of PD-L1 or CTLA-4 on tumor cells. Expression of PD-1 (52.2%), PD-L1 (42.2%) and CTLA-4 (1.6%) on tumor infiltrating T cells was significantly elevated compared to peripheral blood. Of note, PD-1 and PD-L1 were expressed far higher by tumor-infiltrating lymphocytes than CTLA-4. In conclusion, specific immune checkpoint-inhibitors should be evaluated in this disease and the combination with molecular targeted therapies might be of benefit. An extensive immune monitoring should accompany these studies to better understand their mode of action in the tumor microenvironment.Abbreviations: CTLA-4, cytotoxic T lymphocyte associated molecule 4; PBMC, peripheral blood mononuclear cells; PD-1, programmed death 1; PD-L1, programmed death 1 ligand 1; TDLN, tumor-draining lymph nodes; UICC, Union International Contre le Cancer.

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Section: Cd25supporting

confidence: 92%

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

et al. 2015

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“…In recent years, recruitment of regulatory T cells (Tregs) within tumors has been demonstrated to be an immune evasion mechanism [8,9]. Increased numbers of regulatory T cells have been shown in the tumor mucosa of many cancer types, including ovarian cancer, small cell lung cancer, breast cancer, colorectal cancer, and gastric cancer [10][11][12], and Tregs have been associated with poor outcomes in gastric cancer [13,14].…”

Section: Introductionmentioning

confidence: 99%

CD4+ regulatory T cells in gastric cancer mucosa are proliferating and express high levels of IL-10 but little TGF-β

et al. 2016

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“…Numerous studies have shown that CCR7 is differentially expressed in tumor cells in gastric cancer at the mRNA and protein levels, as well as in the cell membrane in vitro and in vivo (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). In addition, CCR7 was detected in tumor-infiltrating lymphocytes and dendritic cells in gastric cancer, as well as in mononuclear cells in Helicobacter pylori gastritis (35,38).…”

Section: C-c Motif Ccr7mentioning

confidence: 99%

C‑C motif chemokine receptors in gastric cancer (Review)

et al. 2017

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Abstract. Gastric cancer is the fifth most common cancer and the third leading cause of cancer-associated mortality worldwide. Despite recent advances in molecular and clinical research, patients with gastric cancer at an advanced stage have a dismal prognosis and poor survival rates, and systemic treatment relies predominantly on traditional cytotoxic chemotherapy. To improve patients' quality of life and survival, an improved understanding of the complex molecular mechanisms involved in gastric cancer progression and treatment resistance, and of its clinical application in the development of novel targeted therapies, is urgently required. Chemokines are a group of small chemotactic cytokines that interact with seven-transmembrane G-protein-coupled receptors, and this interaction serves a crucial role in various physiological processes, including organ development and the host immune response, to recruit cells to specific sites in the body. There is also accumulating evidence that chemokines and chemokine receptors (CCRs) contribute to tumor development and progression, as well as metastasis. However, research regarding the functional roles of chemokines and their receptors in cancer is dynamic and context-dependent, and much remains to be elucidated, although various aspects have been explored extensively. In gastric cancer, C-C motif CCRs are involved in the biological behavior of tumor cells, including the processes of growth, invasion and survival, as well as the epithelial-mesenchymal transition. In the present review, attention is given to the clinical relevance of C-C motif CCRs in the development, progression, and metastasis of gastric cancer, particularly CCR7 and CCR5, which have been investigated extensively, as well as their potential therapeutic implications.

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CCR7 Expression and Intratumoral FOXP3+ Regulatory T Cells are Correlated with Overall Survival and Lymph Node Metastasis in Gastric Cancer

Cited by 44 publications

References 38 publications

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

Immune checkpoints programmed death 1 ligand 1 and cytotoxic T lymphocyte associated molecule 4 in gastric adenocarcinoma

CD4+ regulatory T cells in gastric cancer mucosa are proliferating and express high levels of IL-10 but little TGF-β

C‑C motif chemokine receptors in gastric cancer (Review)

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