scholarly journals The Stromal and Immune Landscape of Nasopharyngeal Carcinoma and Its Implications for Precision Medicine Targeting the Tumor Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Lanqi Gong ◽  
Dora Lai-Wan Kwong ◽  
Wei Dai ◽  
Pingan Wu ◽  
Yan Wang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Tumor Development ◽  
Barr Virus ◽  
Functional Dynamics ◽  
Precision Therapy ◽  
Therapeutic Development ◽  
Complex Ecosystem ◽  
Epstein Barr

The evolution of the tumor microenvironment (TME) is a cancer-dependent and dynamic process. The TME is often a complex ecosystem with immunosuppressive and tumor-promoting functions. Conventional chemotherapy and radiotherapy, primarily focus on inducing tumor apoptosis and hijacking tumor growth, whereas the tumor-protective microenvironment cannot be altered or destructed. Thus, tumor cells can quickly escape from extraneous attack and develop therapeutic resistance, eventually leading to treatment failure. As an Epstein Barr virus (EBV)-associated malignancy, nasopharyngeal carcinoma (NPC) is frequently infiltrated with varied stromal cells, making its microenvironment a highly heterogeneous and suppressive harbor protecting tumor cells from drug penetration, immune attack, and facilitating tumor development. In the last decade, targeted therapy and immunotherapy have emerged as promising options to treat advanced, metastatic, recurrent, and resistant NPC, but lack of understanding of the TME had hindered the therapeutic development and optimization. Single-cell sequencing of NPC-infiltrating cells has recently deciphered stromal composition and functional dynamics in the TME and non-malignant counterpart. In this review, we aim to depict the stromal landscape of NPC in detail based on recent advances, and propose various microenvironment-based approaches for precision therapy.

Towards mapping immune responses of nasopharyngeal carcinoma in Saudi Arabian patients, single institution experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17541-e17541
Author(s):  
Naser Al-Rajhi ◽  
Hussein Soudy ◽  
Shamayel Mohammed ◽  
Hatem Khoja ◽  
Hazem Ghebeh
Keyword(s):  
T Cells ◽  
Nasopharyngeal Carcinoma ◽  
Tumor Cells ◽  
The Other ◽  
Automated System ◽  
Immune Markers ◽  
Barr Virus ◽  
T Cell Infiltration ◽  
Tumor Tissues ◽  
Epstein Barr

e17541 Background: The prevalence of Nasopharyngeal Carcinoma (NPC) is higher in Saudi Arabia compared to western countries. Genetic susceptibility and/or environmental factors (like infection with Epstein-Barr virus) contribute to the development of this tumor. There is a lack of information on the expression of markers related to the immune response in Saudi NPC patients. Methods: Here we report on profiling of two cohorts of NPC cases from patients treated at King Faisal specialist hospital & Research cneter (KFSH&RC) using the most relevant immune markers. The first cohort included 54 patients with local NPC while the other cohort included 25 cases of metastatic NPC at presentation. Immunostaining was done using Ventana benchmark fully automated system. Two anatomical pathologists (SM & HK) scored the NPC cases for CD3+ infiltrating lymphocytes (TIL), and their sub-fractions co-staining for CD8, FOXP3 and/or PD-1. On the other hand, PDL1 expression was assessed on tumor cells. Statistical analysis was done using JUMP Pro 13 software. Results: There was an induction of membranous PDL1 expression on tumor cells of 70 and 64% in local and metastatic cases respectively. Interestingly, there was a significant number of cases with cytoplasmic expression of PDL1 (46% of local and 36% metastatic cases) in addition to the membranous expression. PD-1 was over-expressed (on ≥ 10% of TIL) in 52% and 68% of local and metastatic cases respectively. FOXP3+ T-cells were abundant in the tumor tissues as 78% of cases had ≥10% of their infiltrating CD3+ T-cells co-staining for nuclear FOXP3. Finally, CD8 were an abundant fraction of total CD3+ infiltrating T-cells in more than 60% and 78% of Local and metastatic cohorts respectively. Correlation of the above studied immune markers with patients clinical outcome shows statistically significant correlation (p = 0.008) between low CD3+ T-cell infiltration in tumor tissues at diagnosis and the relapse of the disease. Conclusions: PDL1 is upregulated, FOXP3+ T-regs are abundant, only the low intensity of CD3+ lymphocytes could predict for higher chances of relapse. These preliminary profiling data provide the basis for future immunotherapy trials for NPC in KFSH&RC

scholarly journals Tumor microenvironment contributes to Epstein-Barr virus anti-nuclear antigen-1 antibody production in nasopharyngeal carcinoma

2017 ◽  
Vol 14 (2) ◽  
pp. 2458-2462 ◽  
Author(s):  
Ping Ai ◽  
Zhiping Li ◽  
Yong Jiang ◽  
Changping Song ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Tumor Microenvironment ◽  
Antibody Production ◽  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Modulation of the tumor microenvironment by Epstein-Barr virus latent membrane protein 1 in nasopharyngeal carcinoma

2018 ◽  
Vol 109 (2) ◽  
pp. 272-278 ◽  
Author(s):  
Tomokazu Yoshizaki ◽  
Satoru Kondo ◽  
Kazuhira Endo ◽  
Yosuke Nakanishi ◽  
Mitsuharu Aga ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Tumor Microenvironment ◽  
Membrane Protein ◽  
Epstein Barr Virus ◽  
Latent Membrane Protein ◽  
Latent Membrane Protein 1 ◽  
Barr Virus ◽  
Epstein Barr ◽  
Virus Latent Membrane Protein

scholarly journals Prognostic Value of Epstein-Barr Virus (EBV)-Induced Gene 3 (EBI3) in Diffuse Large B Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5411-5411
Author(s):  
Hong Zheng ◽  
Juan Huang
Keyword(s):  
Tumor Microenvironment ◽  
B Cell ◽  
Tumor Cells ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Barr Virus ◽  
Large B Cell Lymphoma ◽  
Epstein Barr ◽  
Large B Cell

Abstract Background: Epstein-Barr virus (EBV)-induced gene 3 (EBI3) as a subunit for heterodimeric cytokines IL-27 and IL-35, plays important roles both in regulation of T cell proliferation and Th1,Th2 and Th17 cells differentiation. EBI3 was closely related with tumor prognosis. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults with cure-rates of 40-60%. However, Relapse and refractory rate remain in 40% or so. In the present study, we aimed to detect the expression of EBI3 in DLBCL and to analyze its relationship with prognosis. Methods: We retrospective reviewed medical records of 51 newly diagnosed DLBCL patients in Sichuan People's Hospital between January 2010 and December 2016. Immunohistochemical (IHC) assay was used to detect the expression of EBI3 and PD-1 in DLBCL. The expression of CD5, CD30, Bcl-2, Bcl-6, C-myc and Epstein-Barr virus (EBV)-encoded RNAs (EBERs) in tumor specimens from 53 patients was also detected by IHC. The Kaplan-Meier method with log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis. Results: Of the 51 patients, 40 (78.4%) were EBI3-positive in tumor specimens. And PD-1 expression (39/40) was almost in parallel with EBI3 in tumor specimens. EBI3 expression was common in the non-germinal center B-cell-like (GCB) subtype than in the GCB subtype. Patients with EBI3 expression in tumor were more likely to be resistant to first-line chemotherapy when compared with the patients without EBI3 expression in tumor microenvironment (P <0.05). EBI3 expression in tumor microenvironment was correlated with PD-1 expression (r = − 0.20, P = 0.04). Only one patient with EBI3 expression was no PD-1 expression. No correlations were detected between EBI3 expression and the expression of EBER as well as other markers: ALK, CD5, c-Myc and CD30. The complete remission (CR) rates were 7.5% (3/40) and 71.4% in patients with and without EBI3 expression in tumor cells (P = 0.02). EBI3 expression in tumor cells was an independent risk predictor for ORR (P < 0.05). Conclusions: Our results indicate that EBI3 associated with poor prognosis and EBI3 may be a potential therapeutic target and prognosis marker. Disclosures No relevant conflicts of interest to declare.

scholarly journals The association between circulating tumor cells and Epstein-Barr virus activation in patients with nasopharyngeal carcinoma

2017 ◽  
Vol 18 (11) ◽  
pp. 888-894 ◽  
Author(s):  
Caiyun He ◽  
Xinjun Huang ◽  
Xuan Su ◽  
Tao Tang ◽  
Xiao Zhang ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Epstein Barr

Expression of the Epstein-Barr Virus Immediate Early Gene, BZLF1, in Nasopharyngeal Carcinoma Tumor Cells

Virology ◽  
1993 ◽  
Vol 197 (1) ◽  
pp. 358-365 ◽  
Author(s):  
Chantal Cochet ◽  
Dominique Martel-Renoir ◽  
Virginie Grunewald ◽  
Jacques Bosq ◽  
Gilles Cochet ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Tumor Cells ◽  
Epstein Barr Virus ◽  
Immediate Early Gene ◽  
Early Gene ◽  
Immediate Early ◽  
Barr Virus ◽  
Epstein Barr ◽  
Carcinoma Tumor

scholarly journals Spleen Tyrosine Kinase Inhibitor TAK-659 Prevents Splenomegaly and Tumor Development in a Murine Model of Epstein-Barr Virus-Associated Lymphoma

mSphere ◽  
2018 ◽  
Vol 3 (4) ◽  
Author(s):  
Osman Cen ◽  
Karuppiah Kannan ◽  
Jessica Huck Sappal ◽  
Jie Yu ◽  
Mengkun Zhang ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Tumor Cells ◽  
Epstein Barr Virus ◽  
Tumor Development ◽  
Spleen Tyrosine Kinase ◽  
Barr Virus ◽  
Flt3 Inhibitor ◽  
Epstein Barr

ABSTRACTEpstein-Barr virus (EBV) is associated with several B and epithelial cell cancers. EBV-encoded latent membrane protein 2A (LMP2A) contributes to cellular transformation by mimicking B cell receptor signaling. LMP2A/MYC double transgenic mice develop splenomegaly and B cell lymphoma much faster than MYC transgenic mice do. In this study, we explored the potential therapeutic efficacy of a novel spleen tyrosine kinase (SYK) and FLT3 inhibitor TAK-659 for development of a treatment option for EBV-associated malignancies. In our transgenic model, TAK-659 treatment totally abrogated splenomegaly and tumor development in LMP2A/MYC mice in both pretumor and tumor cell transfer experiments. TAK-659 treatment killed tumor cells, but not host cells within the spleen and tumors. Furthermore, TAK-659 treatment abrogated metastasis of tumor cells into bone marrow. Our data also show that TAK-659 inhibits SYK phosphorylation and induces apoptosis in LMP2A/MYC tumor cells at low nanomolar concentrations. Therefore, TAK-659 may provide an effective therapeutic option for treatment of LMP2A-positive EBV-associated malignancies and should be explored further in clinical trials.IMPORTANCEThe novel SYK and FLT3 inhibitor TAK-659 prevents the enlargement of spleen and tumor development in a mouse model of EBV-associated lymphoma by counteracting the activation of cellular kinase SYK through the viral LMP2A gene by inducing cell death in tumor cells but not in nontumor cells. These findings indicate that TAK-659 may be a very effective nontoxic therapeutic molecule especially for EBV-positive hematologic malignancies.

Advances in research on microRNAs related to the invasion and metastasis of nasopharyngeal carcinoma

2021 ◽  
Vol 14 ◽  
Author(s):  
ShanShan Zhang ◽  
BaiQi Wang ◽  
LuLu Zheng ◽  
ZhuQiong Fu ◽  
YiTing Fu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Tumor Development ◽  
Epstein Barr Virus Infection ◽  
Cellular Mirnas ◽  
Biological Targets ◽  
Barr Virus ◽  
Epstein Barr ◽  
Barr Virus Infection ◽  
Molecular Aberrations

: Nasopharyngeal carcinoma (NPC), which is associated with latent Epstein-Barr virus infection in most cases, is a unique epithelial malignancy arising from the nasopharyngeal mucosal lining. Accumulating evidence provides insights into the genetic and molecular aberrations that likely drive nasopharyngeal tumor development and progression. We review recent analyses of microRNAs (miRNAs), including Epstein-Barr virus-encoded miRNAs (EBV-encoded miRNAs) and dysregulated cellular miRNAs, that may be related to the metastasis of nasopharyngeal carcinoma. The studies summarized herein have greatly expanded our knowledge of the molecular biology of NPC involving miRNAs, and they may provide new biological targets for clinical diagnosis and reveal the potential of microRNA therapeutics. However, much information remains to be uncovered.

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