Knockdown of HVEM, a Lymphocyte Regulator Gene, in Ovarian Cancer Cells Increases Sensitivity to Activated T Cells

Zhang, Ting; Ye, Lei; Han, Lu; He, Qizhi; Zhu, Jianlong

doi:10.3727/096504016x14641336229602

Cited by 22 publications

(19 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, enhancing BTLA/HVEM interaction could reduce the proliferation and differentiation of Vγ9Vδ2 T cells that are involved in tumor immune surveillance. 24 Zhang et al 8 reported that overexpression of HVEM in ovarian cancer cells inhibited proliferation and immune functions of T cells, while HVEM-silenced cancer cells had increased the number of activated T cells as well as the secretion of TNF-α and IFN-γ, which in turn promoted apoptosis of cancer cells. In general, the above data suggested that BTLA and HVEM may be important factors in the physiopathology of immune regulation and may also have an effect on tumor progression and prognosis.…”

Section: Discussionmentioning

confidence: 99%

Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis

Lan¹,

Li²,

Gao³

et al. 2017

OTT

View full text Add to dashboard Cite

PurposeDeregulation of immune checkpoint molecules by tumor cells is related to immune escape. This study was conducted to investigate the relationship between the appearance of B- and T-lymphocyte attenuator (BTLA) and its ligand herpesvirus entry mediator (HVEM) with the prognosis in gastric cancer patients.Patients and methodsA total of 136 patients with curative gastrectomy were included. The expression of BTLA and HVEM was detected by immunohistochemistry, and its correlation with the clinical significance of gastric cancer was further analyzed.ResultsThe positivity of BTLA and HVEM was detected in 74.3% (101/136) and 89.0% (121/136) of the gastric cancer specimens, respectively. A high expression of BTLA and HVEM was detected, respectively, in 28.7% (39/136) and 44.9% (61/136) of the specimens. Characteristics analysis showed that the high expression of BTLA was significantly associated with lymph node metastasis (P=0.030). Similarly, the high expression of HVEM was also significantly correlated with lymph node metastasis (P=0.007) and depth of invasion (P=0.011). In addition, there was a positive correlation between the expression of BTLA and HVEM in gastric cancer specimens (r=0.245, P=0.004). Univariate analysis revealed that the high expression of BTLA and HVEM was associated with overall survival of patients along with tumor size, Borrmann type, depth of invasion, lymph node metastasis, and histological grade (P<0.05). Multivariate analysis established that the high expression of HVEM (P=0.010), depth of invasion (P=0.001), lymph node metastasis (P<0.001), and histological grade (P=0.027) were independent prognostic factors associated with overall survival in patients with gastric cancer.ConclusionThe increased BTLA and HVEM levels correlate with the development and poor prognosis of gastric cancer. HVEM is an important prognostic indicator, and BTLA/HVEM pathway is considered to be a promising candidate for immunotherapy of gastric cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis

Lan¹,

Li²,

Gao³

et al. 2017

OTT

View full text Add to dashboard Cite

show abstract

“…Moreover, carcinomas with a higher HVEM expression display lower TILs infiltration and worse prognosis. Similarly, in ovarian cancer, HVEM mRNA was up-regulated compared with nonmalignant tissues (98). Silencing HVEM on ovarian cancer cells by shRNA knock-down increased T cellinduced apoptosis of cancer cells in vitro.…”

Section: B7-h4 (Alternatively Called B7x or B7s1)mentioning

confidence: 91%

Immune ligands for cytotoxic T Lymphocytes CTLS in cancer stem cells CSCS

Voutsadakis¹

2018

Front Biosci

View full text Add to dashboard Cite

The immune system has come to the forefront of cancer therapeutics in recent years with the success of immune blockade inhibitors in a variety of cancers whose list is increasing with a quick pace. Despite the efficacy of these drugs across a significant part of the cancer spectrum, responses are still seen only in a minority of patients, that implies that most patients are refractory or promptly develop resistance to these agents. Mechanisms of this resistance are important to decipher as this knowledge may lead to the introduction of additional therapies or manipulations to modulate resistance. The cancer stem cell theory stipulates that a minority of cancer cells in a given tumor are responsible for self-renewal and bulk tumor propagation. These cells, in most instances, are rare and less proliferative but give rise to highly proliferative progeny. In addition, they are, in general, resistant to therapies and endowed with metastatic potential through a process called EMT (Epithelial to Mesenchymal Transition). Cancer stem cells resistance to treatments may relate to inherent insensitivity to external apoptotic stimuli and, thus, may extend to immune therapies by inhibiting the actions of Cytotoxic T Lymphocytes (CTLs) in the tumor micro-environment. This paper examines available data on expression and regulation of immune co-modulatory (co-stimulatory and co-inhibitory) ligands on cancer stem cells in order to devise strategies to circumvent resistance.

show abstract

“…In our previous study, HVEM was found highly expressed in the ovarian cancer tissues compared with normal tissues [18]. Moreover, HVEM was correlated to TNM stage, lymph node metastasis and recurrence in ovarian serous adenocarcinoma [17].…”

Section: Hvem Co-expressed With Hif-1α In Patients With Ovarian Cancermentioning

confidence: 99%

“…In our previous finding, we showed that the expression of HVEM was significantly high in ovarian cancer tissues and was closely correlated to the clinical pathological features of the patient, including the clinical stage (FIGO2013), lymph-node metastasis and recurrence [17]. However, the overexpression of HVEM had no effects on the cell multiplication in normoxic ovarian cancer cells [18]. In this work, we investigated the role of HVEM in hypoxic ovarian cancer cells and the relationship between HVEM and HIF-1α by overexpressing and silencing HVEM.…”

Section: Introductionmentioning

confidence: 97%

HVEM/HIF-1α promoted proliferation and inhibited apoptosis of ovarian cancer cells under hypoxic microenvironment conditions

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: Our previous studies showed the expression of herpes virus entry mediator (HVEM) is high in ovarian cancer samples and correlated to the patient clinic pathological features. As we all know, the hypoxic environment is the main feature of tumor. In this work, we explored the role of HVEM in hypoxic ovarian cancer cells and its effects on HIF-1α, a transcription factor responding to hypoxia. Methods: The expression of HVEM, HIF-1α and apoptosis-related genes was detected by qRT-PCR and western blot. The proliferation and apoptosis of the ovarian cancer cells were determined with the Cell Counting Kit-8 assay and AnnexinV-FITC/PI-stained flow cytometry assay, respectively. Results: The expression of HVEM was positively correlated to that of HIF-1α. The expression of HVEM and HIF-1α under hypoxic conditions was higher than that under normoxic conditions, which suggested that the level of HVEM and HIF-1α correlates with prolonged periods of hypoxia in ovarian cancer. The overexpression of HVEM promoted cell proliferation and inhibited cell apoptosis under hypoxic condition. HVEM overexpression elevated the expression of HIF-1α and Bcl-2 (anti-apoptotic protein), and reduced the expression of Bax (pro-apoptotic protein). In addition, overexpression of HVEM activated the AKT/mTOR signaling. Moreover, knockdown of HVEM had the completely opposite effects. Conclusion: These data indicated that HVEM signaling might promote HIF-1α activity via AKT/mTOR signaling pathway and thus to regulate tumor growth in ovarian cancer under the hypoxic conditions. Furthermore, these findings indicate that this molecular mechanism could represent a therapeutic target for ovarian cancer.

show abstract

Knockdown of HVEM, a Lymphocyte Regulator Gene, in Ovarian Cancer Cells Increases Sensitivity to Activated T Cells

Cited by 22 publications

References 16 publications

Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis

Increased BTLA and HVEM in gastric cancer are associated with progression and poor prognosis

Immune ligands for cytotoxic T Lymphocytes CTLS in cancer stem cells CSCS

HVEM/HIF-1α promoted proliferation and inhibited apoptosis of ovarian cancer cells under hypoxic microenvironment conditions

Contact Info

Product

Resources

About