The Role of NK Cells in EBV Infection and EBV-Associated NPC

Abstract

A vast majority of the population worldwide are asymptomatic carriers of Epstein-Barr Virus (EBV). However, some infected individuals eventually develop EBV-related cancers, including Nasopharyngeal Carcinoma (NPC). NPC is one of the most common EBV-associated epithelial cancers, and is highly prevalent in Southern China and Southeast Asia. While NPC is highly sensitive to radiotherapy and chemotherapy, there is a lack of effective and durable treatment among the 15%–30% of patients who subsequently develop recurrent disease. Natural Killer (NK) cells are natural immune lymphocytes that are innately primed against virus-infected cells and nascent aberrant transformed cells. As EBV is found in both virally infected and cancer cells, it is of interest to examine the NK cells’ role in both EBV infection and EBV-associated NPC. Herein, we review the current understanding of how EBV-infected cells are cleared by NK cells, and how EBV can evade NK cell-mediated elimination in the context of type II latency in NPC. Next, we summarize the current literature about NPC and NK cell biology. Finally, we discuss the translational potential of NK cells in NPC. This information will deepen our understanding of host immune interactions with EBV-associated NPC and facilitate development of more effective NK-mediated therapies for NPC treatment.

Distribution of CD8 T Cells and NK Cells in the Stroma in Relation to Recurrence or Metastasis of Nasopharyngeal Carcinoma

“… 36 Similar to CD8 T cells, NK cells target virus-infected cells, but through germline-encoded receptors, unlike CD8 T cells. 37 …”

“…36 Similar to CD8 T cells, NK cells target virus-infected cells, but through germline-encoded receptors, unlike CD8 T cells. 37 Macrophages are an abundant population of TIICs in TMEs. 38 Under different stimulations, macrophages M0 can differentiate into two further phenotypes: antitumor M1 and pro-tumor M2.…”

Immunosuppressive Tumor Microenvironment and Immunotherapy of Epstein–Barr Virus-Associated Malignancies

“…The EBV-encoded miRNAs, such as miRNA-BARTs, can dull NK cell immune recognition, and impair NK cell cytotoxic response by diminishing IL-12 release [ 73 , 74 ]. In such ways, the EBV weakens the antitumor function of NK cells and contributes to immune evasion in EBV-positive malignancies [ 75 ].…”

The emergence of tumor-infiltrating lymphocytes in nasopharyngeal carcinoma: Predictive value and immunotherapy implications

“… Good prognosis 15 , 25 FoxP3 + Treg Secrete cytokines such as IL-2, IL-4, TNF-α, IL-17, IL-10, IFN-γ Inhibit the function of effector cells or effector molecules. Poor prognosis 37 , 73 , 94 CD56 NK Recognize NKG2D homodimers and natural cytotoxic receptors Cytotoxic functions without prior sensitization Good prognosis 11 , 95 , 96 M1 Express CD163, CD206 and CD204 markers, and secrete Th2 cytokines Promoting anti-tumor TH1 and TH17 immune responses Good prognosis 97 M2 Secrete TH1 cytokines such as TNF-α, IL-12, and small amounts of IL-10 and IL-4 Supporting angiogenesis, tumor progression, and metastasis; Poor prognosis 36 , 98 DC Activate the initial T cells and CD8 + T cells and secrete a variety of cytokines and chemokines Binary immune regulatory function shaped by TME. Ambiguous 99 MDSCs Differentiating into TAMs, secreting cytokines (TGF-β/IL-10) and inhibiting T cell activation Promote tumor growth Poor prognosis 23 , 100 …”