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

2014 ◽  
Vol 110 (6) ◽  
pp. 1552-1560 ◽  
Author(s):  
G-F Ma ◽  
Q Miao ◽  
Y-M Liu ◽  
H Gao ◽  
J-J Lian ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Foxp3 Expression ◽  
Tumour Microenvironment ◽  
Tumour Cells

scholarly journals Comprehensive Characterization of Tumor Purity and Its Clinical Implications in Gastric Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Shenghan Lou ◽  
Jian Zhang ◽  
Xin Yin ◽  
Yao Zhang ◽  
Tianyi Fang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Mechanisms ◽  
Comprehensive Evaluation ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Patient Specific ◽  
Validity And Reliability ◽  
Cell Functions

Solid tumour tissues are composed of tumour and non-tumour cells, such as stromal cells and immune cells. These non-tumour cells constitute an essential part of the tumour microenvironment (TME), which decrease the tumour purity and play an important role in carcinogenesis, malignancy progression, treatment resistance and prognostic assessment. However, the implications of various purity levels in gastric cancer (GC) remain largely unknown. In the present study, we used an in-silico approach to infer the tumour purity of 2,259 GC samples obtained from our hospital and 12 public datasets based on the transcriptomic data. We systematically evaluated the association of tumour purity with clinical outcomes, biological features, TME characteristics and treatment response in GC. We found that tumour purity might be a patient-specific intrinsic characteristic of GC. Low tumour purity was independently correlated with shorter survival time and faster recurrence and significantly associated with mesenchymal, invasive and metastatic phenotypes. Integrating GC purity into a clinical prognostic nomogram significantly improved predictive validity and reliability. In addition, low tumour purity was strongly associated with immune and stromal cell functions. Fibroblasts, endothelial cells and monocytes were markedly enriched in low-purity tumours, serving as robust indicators of a poor prognosis. Moreover, patients with low GC purity may not benefit more from adjuvant chemotherapy. Our findings highlight that tumour purity confers important clinical, biological, microenvironmental and treatment implications for patients with GC. Therefore, a comprehensive evaluation of tumour purity in individual tumours can provide more insights into the molecular mechanisms of GC, facilitate precise classification and clinical prediction and help to develop more effective individualised treatment strategies.

scholarly journals Exosome-derived noncoding RNAs in gastric cancer: functions and clinical applications

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiao-Huan Tang ◽  
Ting Guo ◽  
Xiang-Yu Gao ◽  
Xiao-Long Wu ◽  
Xiao-Fang Xing ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Noncoding Rnas ◽  
Tumour Microenvironment ◽  
Clinical Applications ◽  
Biological Molecules ◽  
Biological Functions ◽  
Membrane Structures ◽  
Chemical Substances ◽  
Expression Levels ◽  
The Stability

AbstractExosomes are a subpopulation of the tumour microenvironment (TME) that transmit various biological molecules to promote intercellular communication. Exosomes are derived from nearly all types of cells and exist in all body fluids. Noncoding RNAs (ncRNAs) are among the most abundant contents in exosomes, and some ncRNAs with biological functions are specifically packaged into exosomes. Recent studies have revealed that exosome-derived ncRNAs play crucial roles in the tumorigenesis, progression and drug resistance of gastric cancer (GC). In addition, regulating the expression levels of exosomal ncRNAs can promote or suppress GC progression. Moreover, the membrane structures of exosomes protect ncRNAs from degradation by enzymes and other chemical substances, significantly increasing the stability of exosomal ncRNAs. Specific hallmarks within exosomes that can be used for exosome identification, and specific contents can be used to determine their origin. Therefore, exosomal ncRNAs are suitable for use as diagnostic and prognostic biomarkers or therapeutic targets. Regulating the biogenesis of exosomes and the expression levels of exosomal ncRNAs may represent a new way to block or eradicate GC. In this review, we summarized the origins and characteristics of exosomes and analysed the association between exosomal ncRNAs and GC development.

scholarly journals Therapeutic Targeting of the Tumour Microenvironment in Metastatic Colorectal Cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 2067
Author(s):  
Rhynelle S. Dmello ◽  
Sarah Q. To ◽  
Ashwini L. Chand
Keyword(s):  
Colorectal Cancer ◽  
Targeted Therapy ◽  
Liver Metastasis ◽  
Metastatic Colorectal Cancer ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Cellular Interactions ◽  
Circulating Tumour Cells ◽  
Therapeutic Targeting ◽  
Colorectal Cancer Patients

Liver metastasis is the primary contributor to the death of patients with colorectal cancer. Despite the overall success of current treatments including targeted therapy, chemotherapy, and immunotherapy combinations in colorectal cancer patients, the prognosis of patients with liver metastasis remains poor. Recent studies have highlighted the importance of the tumour microenvironment and the crosstalk within that determines the fate of circulating tumour cells in distant organs. Understanding the interactions between liver resident cells and tumour cells colonising the liver opens new therapeutic windows for the successful treatment of metastatic colorectal cancer. Here we discuss critical cellular interactions within the tumour microenvironment in primary tumours and in liver metastases that highlight potential therapeutic targets. We also discuss recent therapeutic advances for the treatment of metastatic colorectal cancer.

scholarly journals Association between the exposure to anti-angiogenic agents and tumour immune microenvironment in advanced gastrointestinal stromal tumours

2019 ◽  
Vol 121 (10) ◽  
pp. 819-826 ◽  
Author(s):  
Changhoon Yoo ◽  
Yeon-mi Ryu ◽  
Sang-Yeob Kim ◽  
Jihun Kim ◽  
Chan Young Ock ◽  
...  
Keyword(s):  
T Cells ◽  
Tyrosine Kinase Inhibitor ◽  
Kinase Inhibitor ◽  
Foxp3 Expression ◽  
Treated Group ◽  
Tumour Cells ◽  
Gastrointestinal Stromal Tumours ◽  
Immune Microenvironment ◽  
Treatment Groups ◽  
Expression Rate

Abstract Background Tumour immune microenvironment (TIME) of gastrointestinal stromal tumours (GISTs) is largely unknown. Methods A total of 81 surgical specimens from 67 patients with advanced GISTs were categorised into treatment groups: tyrosine kinase inhibitor (TKI)-naive, n = 20; imatinib-progressed and no exposure to sunitinib or regorafenib (IM-PD), n = 30; and imatinib-progressed and sunitinib and/or regorafenib-treated (IM-PD/SU-treated), n = 31. Multiplexed immunofluorescence staining and RNA sequencing were performed to define TIME. Results PD-L1 expression rate (>1%) of DOG-1+ tumour cells was 5.0, 6.7, and 29.0% in TKI-naive, IM-PD, and IM-PD/SU-treated group, respectively (p = 0.02). FoxP3 expression of CD3+ T cells and CD204+ CD68+ monocytes per DOG-1+ cells was significantly higher in IM-PD/SU-treated group compared to TKI-naive and IM-PD groups (p < 0.05). IM-PD/SU-treated group showed increased expression of PD-1 on CD3+ T cells (p = 0.03 vs TKI-naive; p = 0.003 vs IM-PD) and DOG-1+ tumour cells (p = 0.02 vs TKI-naive; p = 0.006 vs IM-PD), TIM-3 expression on CD3+ T cells (p = 0.01 vs TKI-naive; p = 0.002 vs IM-PD), and LAG3 expression on CD3+ T cells (p = 0.001 vs TKI-naive; p = 0.004 vs IM-PD). In the RNAseq analysis, TIGIT expression was significantly increased in IM-PD/SU-treated GISTs compared to IM-PD (p = 0.01). Conclusion Immunosuppressive phenotype was predominant in tumours treated with anti-angiogenic agents compared to TKI-naive and IM-treated tumours.

616. The relation between HER2 overexpression on the tumour cells and microvessels density in the tumour stroma in gastric cancer

2016 ◽  
Vol 42 (9) ◽  
pp. S184
Author(s):  
M. Ciesielski ◽  
M. Szajewski ◽  
W.J. Kruszewski ◽  
R. Pęksa ◽  
J. Zieliński ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumour Cells ◽  
Her2 Overexpression ◽  
Tumour Stroma ◽  
Microvessels Density

Identification and validation of tumour microenvironment-based immune molecular subgroups for gastric cancer: immunotherapeutic implications

2020 ◽  
Vol 69 (6) ◽  
pp. 1057-1069 ◽  
Author(s):  
Yu-Jie Zhou ◽  
Gui-Qi Zhu ◽  
Xiao-Fan Lu ◽  
Kenneth I. Zheng ◽  
Qi-Wen Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumour Microenvironment ◽  
Molecular Subgroups ◽  
Cancer Immunotherapeutic

Treg phenotype in T-cell lymphomas

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18513-18513
Author(s):  
D. Morales ◽  
B. E. Beltran ◽  
C. Castañeda ◽  
A. Carrasco ◽  
P. Quiñones ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lymphoma ◽  
Foxp3 Expression ◽  
Tumour Cells ◽  
T Cell Lymphoma ◽  
Immunohistochemical Method ◽  
Cytotoxic T Cell ◽  
T Cell Lymphomas ◽  
Treg Phenotype

18513 Background: Foxp3 is a key regulatory gene required for the development and function of: regulatory CD4+CD25high T cells (Treg) specialized in maintaining the balance between immunity and tolerance and activated conventional CD4+CD25low T cells without suppressive activity. Previous studies had reported the origin of Adult T-cell Leukemia/Lymphoma cells (ATLL) in Foxp3 T cells and in other lymphomas types the FOXP3 expression was only detected in the reactive T-cell background. Our objetive was to determine the presence of Treg phenotype cells by the FOXP3 expression in T-cell lymphomas. Methods: A retrospective study was performed on 48 samples collected from diverse T-cell lymphomas in our institution. A highly sensitive immunohistochemical method was used to demonstrate Treg phenotype by FOXP3 protein expression with a mouse monoclonal antibody (clone 236A/E7ABCAM) in most formalin-fixed paraffin-embedded tissue sections from lymph nodes, skin, bone marrow and extranodal sites samples as cavum and stomach. We did not co-stained with CD25 and considered a FOXP3+ tissue when positivity was > 20% of tumor cells. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: Among the 48 evaluable T-cell lymphomas collected, 33 were ATLL, 8 unspecified peripheral T-cell lymphomas (U-PTCL), 6 mycosis fungoides (MF) and 1 cutaneous aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma. Among the 33 ATLL: lymphomatous=17, acute=11, smoldering=1, chronic=1, cutaneous=1 and undefined=2. FOXP3 expression in tumour cells was detected in 24% (8/33) of ATLL cases and in 37% (3/8) of U-PTCL. It was negative in MF tumour cells and aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma Among the ATLL cases FOXP3 positivity were obtained in 35% (6/17) of lymphomatous type; 18% (2/11) of acute ones and none in others ATLL types studied. Interestingly 3 U-PTCL had Treg phenotype and were related to EBV (LMP1 positive); two had extranodal primary ( parotide and cavum) and one was nodal. We failed to demonstrate any correlation between FOXP3 status and survival. Conclusions: Some ATLL and U-PTCL had Treg phenotype. In our work Foxp3 expression was not found to be a prognostic factor. No significant financial relationships to disclose.

scholarly journals Activation of blood coagulation in cancer: implications for tumour progression

2013 ◽  
Vol 33 (5) ◽  
Author(s):  
Luize G. Lima ◽  
Robson Q. Monteiro
Keyword(s):  
Blood Coagulation ◽  
Tumour Progression ◽  
Primary Tumour ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Protease Activated Receptors ◽  
Tumour Metastasis ◽  
Coagulation Proteins ◽  
Associated Proteins ◽  
Cancer Associated Thrombosis

Several studies have suggested a role for blood coagulation proteins in tumour progression. Herein, we discuss (1) the activation of the blood clotting cascade in the tumour microenvironment and its impact on primary tumour growth; (2) the intravascular activation of blood coagulation and its impact on tumour metastasis and cancer-associated thrombosis; and (3) antitumour therapies that target blood-coagulation-associated proteins. Expression levels of the clotting initiator protein TF (tissue factor) have been correlated with tumour cell aggressiveness. Simultaneous TF expression and PS (phosphatidylserine) exposure by tumour cells promote the extravascular activation of blood coagulation. The generation of blood coagulation enzymes in the tumour microenvironment may trigger the activation of PARs (protease-activated receptors). In particular, PAR1 and PAR2 have been associated with many aspects of tumour biology. The procoagulant activity of circulating tumour cells favours metastasis, whereas the release of TF-bearing MVs (microvesicles) into the circulation has been correlated with cancer-associated thrombosis. Given the role of coagulation proteins in tumour progression, it has been proposed that they could be targets for the development of new antitumour therapies.

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