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Review
. 2023 Jan 11:13:1079515.
doi: 10.3389/fimmu.2022.1079515. eCollection 2022.

Immunotherapeutic approaches in EBV-associated nasopharyngeal carcinoma

Wenting Li  1 , Xiaobing Duan  1 , Xingxing Chen  2 , Meixiao Zhan  1 , Haichuan Peng  1 , Ya Meng  1   3 , Xiaobin Li  1 , Xian-Yang Li  1   4 , Guofu Pang  2 , Xiaohui Dou  1   5
Affiliations
Review

Immunotherapeutic approaches in EBV-associated nasopharyngeal carcinoma

Wenting Li et al. Front Immunol. .

Abstract

Epstein-Barr virus (EBV) was the first tumor virus in humans. Nasopharyngeal carcinoma (NPC) accounts for approximately 60% of the 200,000 new tumor cases caused by EBV infection worldwide each year. NPC has an insidious onset and is highly malignant, with more than 70% of patients having intermediate to advanced disease at the time of initial diagnosis, and is strongly implicated in epithelial cancers as well as malignant lymphoid and natural killer/T cell lymphomas. Over 90% of patients with confirmed undifferentiated NPC are infected with EBV. In recent decades, much progress has been made in understanding the molecular mechanisms of NPC and developing therapeutic approaches. Radiotherapy and chemotherapy are the main treatment options for NPC; however, they have a limited efficacy in patients with locally advanced or distant metastatic tumors. Tumor immunotherapy, including vaccination, adoptive cell therapy, and immune checkpoint blockade, represents a promising therapeutic approach for NPC. Significant breakthroughs have recently been made in the application of immunotherapy for patients with recurrent or metastatic NPC (RM-NPC), indicating a broad prospect for NPC immunotherapy. Here, we review important research findings regarding immunotherapy for NPC patients and provide insights for future research.

Keywords: EBV-associated cancer; EBV-directed vaccination; Epstein-Barr virus; TCR-T therapy; adoptive cell therapy; immune checkpoint inhibitors.

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Conflict of interest statement

X-YL is an employee of OriCell Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Graphical summary of EBV infected epithelial cells, B cells, and NK/T cell. EBV primarily infects epithelial and B cells. Infection with EBV may cause many human cancers, including epithelial cancers such as EBVaGC, NPC, EBVaICC, and pLELC. EBV-infected B cells can lead to malignant lymphomas, such as DLBL, PTLD, and BL. Similarly, EBV infects NK/T cells to form NK/T cell lymphomas. EBV establishes a persistent latent infection in malignant epithelial cells (known as latency I, latency II, and latency III). All EBV-associated epithelial cancers express a latency II program (–12). Two therapeutic vaccines have been investigated for NPC, namely, peptide-based vaccines and DC vaccines. EBV requires a variety of envelope proteins to enter cells. The membrane proteins gp350, gH/gL, gB, and gp42 are required for B cell infection, whereas BMFR2, gH/gL, and gB are needed for epithelial cell infection. Another vaccine under study mainly uses LMP1, LMP2, EBNA1 and EBNA3 as target antigens to construct viral vaccines by single or multiple protein combinations. Figure was created with BioRender.
Figure 2
Figure 2
Treatment of NPC. Different stages of NPC have different treatment methods. The traditional treatment of NPC includes surgery, radiotherapy, chemotherapy, and targeted therapy. Immunotherapy is a promising therapeutic approach for NPC treatment. Figure was created with BioRender.
Figure 3
Figure 3
Illustration of major modalities of tumor immunotherapy for NPC. Primary strategies of tumor immunotherapy for NPC include EBV-directed vaccination (A), EBV-CTLs intravenous infusion (B), and immune checkpoint blockade (C). Figure was created with BioRender.
Figure 4
Figure 4
Comparison of CAR-T and TCR-T cells in the treatment of NPC. Engineered immune cell therapy works by modifying immune cells so that they can recognize disease states and respond appropriately. When engineered immune cells are transferred into patient, they are a “living drug”. TCR-T is similar to CAR-T in that it involves engineering a patient’s own T lymphocytes and then injecting back into the patient. The procedure mainly includes: extraction of patients’ peripheral blood, isolation of PBMC, engineering of immune cells, amplification of immune cells and cell transfusions into patients. Figure was created with BioRender.
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Grants and funding

This study was supported by research grants from the National Natural Science Foundation of China (No. 82230067, 81902936, 82003450, 82103433), Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment (2021B1212040004), Guangdong Basic and Applied Basic Research Foundation (No. 2020B1515020010, 2020A1515110013, 2022B1515020010), and Zhuhai Science and Technology Planning Medical and Health Project (No. ZH22036201210108PWC).

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