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Cancers
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New Therapies and Immunological Findings in Nasopharyngeal Carcinoma
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New Therapies and Immunological Findings in Nasopharyngeal Carcinoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 9564

Special Issue Editors

Prof. Dr. Dora Kwong

E-Mail Website
Guest Editor
Department of Clinical Oncology, Centre of Cancer Medicine, Li Ka Shing School of Medicine, The University of Hong Kong, Hong Kong
Interests: nasopharyngeal carcinoma, tumor microenvironment; adoptive T cell therapy
Dr. Darren Wan Teck Lim

E-Mail Website
Guest Editor
Division of Medical Oncology, National Cancer Centre Singapore, Duke-NUS Medical School, Singapore
Interests: nasopharyngeal and head neck squamous cancers; lung cancer; immunotherapy resistance and circulating biomarkers

Special Issue Information

Dear Colleagues,

We are pleased to invite you to contribute to this Special Issue on “New Therapies and Immunological Findings in Nasopharyngeal Carcinoma”. Endemic nasopharyngeal carcinoma is associated with Epstein–Barr virus (EBV) and the reports of abundant lymphocyte infiltration in the tumor strongly suggest that it is an immune-elated cancer. There is a long history of clinical trials using immunotherapy in NPC. Various attempts at targeting the EBV, including the EBV vaccine and EBV-specific T cells therapy, had only limited success. While immunotherapy using checkpoint inhibitors and CAR-T cell therapy had firmly been established as a standard of care in other cancers, the advances in immunotherapy for NPC have lagged behind. Single-agent PD-1 inhibitors have limited efficacy in chemotherapy-resistant disease. While combined treatment with chemotherapy and PD-1 inhibitors was shown to improve responses and disease-free survival in first-line settings of metastatic disease, there is no biomarker that can predict patient responses to treatment. Thus, there is an urgent need to review our current knowledge on the immunology and immunotherapy of NPC and to search for new directions to improve the current therapeutics.

This Special Issue aims to review our knowledge on immune biology and to report new immune therapeutics for NPC. The scope will include revisiting the role of EBV, identifying potential pathways that cause T cell exhaustion and immune evasion, looking for new targets for immune therapy and immune modulation and identification of biomarkers for predicting response to checkpoint inhibitors or cellular therapy.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: studies on the tumor microenvironment and systemic immunology, reports on neoantigens and novel targets for immunotherapy. We also call for reports on pre-clinical studies on new immunotherapy. Reports from early phase clinical trials and their correlative laboratory findings, especially on predictive biomarkers, are most welcome.

We look forward to receiving your contributions.

Prof. Dr. Dora Kwong
Dr. Darren Wan Teck Lim
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • EBV
  • tumor microenvironment
  • neoantigens
  • checkpoint inhibitors
  • cellular immunotherapy
  • vaccine
  • biomarkers

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Published Papers (4 papers)

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Research

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13 pages, 1225 KiB  
Article
A Joint Model Based on Post-Treatment Longitudinal Prognostic Nutritional Index to Predict Survival in Nasopharyngeal Carcinoma
by Po-Wen Hsiao, Yu-Ming Wang, Shao-Chun Wu, Wei-Chih Chen, Ching-Nung Wu, Tai-Jan Chiu, Yao-Hsu Yang and Sheng-Dean Luo
Cancers 2024, 16(5), 1037; https://doi.org/10.3390/cancers16051037 - 3 Mar 2024
Cited by 1 | Viewed by 1407
Abstract
Background: a low PNI in patients with NPC is linked to poor survival, but prior studies have focused on single-timepoint measurements. Our study aims to employ joint modeling to analyze longitudinal PNI data from each routine visit, exploring its relationship with overall survival. [...] Read more.
Background: a low PNI in patients with NPC is linked to poor survival, but prior studies have focused on single-timepoint measurements. Our study aims to employ joint modeling to analyze longitudinal PNI data from each routine visit, exploring its relationship with overall survival. Methods: In this retrospective study using data from the Chang Gung Research Database (2007–2019), we enrolled patients with NPC undergoing curative treatment. We analyzed the correlation between patient characteristics, including the PNI, and overall survival. A joint model combining a longitudinal sub-model with a time-to-event sub-model was used to further evaluate the prognostic value of longitudinal PNI. Results: A total of 2332 patient were enrolled for the analysis. Separate survival analyses showed that longitudinal PNI was an independent indicator of a reduced mortality risk (adjusted HR 0.813; 95% CI, 0.805 to 0.821). Joint modeling confirmed longitudinal PNI as a consistent predictor of survival (HR 0.864; 95% CI, 0.850 to 0.879). An ROC analysis revealed that a PNI below 38.1 significantly increased the risk of 90-day mortality, with 90.0% sensitivity and 89.6% specificity. Conclusions: Longitudinal PNI data independently predicted the overall survival in patients with NPC, significantly forecasting 90-day survival outcomes. We recommend routine PNI assessments during each clinic visit for these patients. Full article
(This article belongs to the Special Issue New Therapies and Immunological Findings in Nasopharyngeal Carcinoma)
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21 pages, 7099 KiB  
Article
Shift in Tissue-Specific Immune Niches and CD137 Expression in Tuberculoma of Pembrolizumab-Treated Nasopharyngeal Carcinoma Patients
by Ngar Woon Kam, Anthony Wing Ip Lo, Desmond Tae Yang Hung, Ho Ko, Ka Chun Wu, Dora Lai Wan Kwong, Ka On Lam, To Wai Leung, Chi Ming Che and Victor Ho Fun Lee
Cancers 2024, 16(2), 268; https://doi.org/10.3390/cancers16020268 - 8 Jan 2024
Cited by 1 | Viewed by 2164
Abstract
The use of immune checkpoint inhibitors (ICIs) in cancer treatment has shown promise but can also have unintended consequences, such as reactivating latent tuberculosis (TB). To develop treatments that address ICIs-related adverse events, it is essential to understand cellular heterogeneity across healthy and [...] Read more.
The use of immune checkpoint inhibitors (ICIs) in cancer treatment has shown promise but can also have unintended consequences, such as reactivating latent tuberculosis (TB). To develop treatments that address ICIs-related adverse events, it is essential to understand cellular heterogeneity across healthy and pathological tissues. We performed cross-tissue multiplexed staining analysis on samples from two patients with TB reactivation during pembrolizumab treatment for metastatic nasopharyngeal carcinoma. CD8+ T cells, rather than CD4+ T cells, accumulated preferentially in the tuberculoma and were associated with increased production of IFNγ and expression of CD137. Additionally, CD137 enrichment played a role in the spatial organization of the tuberculoma, with specific interaction limited to spatial proximal cells between IFNγ+ CD137+ CD8+ T cells and IL12+ CD137+ type-1 macrophages. This unique feature was not observed in non-tumoral or tumoral tissues. Our analysis of public transcriptomic datasets supported the notion that this cellular interaction was more prominent in patients with durable ICI responses compared to those with non-ICI-related TB. We suggest that shifts towards CD137-rich immune niches are correlated with both off-target immune-related adverse events and anti-tumor efficacy. Targeting the tumor microenvironment through conditional activation of anti-CD137 signaling in combination with ICIs can modulate the reactivity of T cells and macrophages for localized tumor killing without the potential off-target immune-related risks associated with ICIs alone. Full article
(This article belongs to the Special Issue New Therapies and Immunological Findings in Nasopharyngeal Carcinoma)
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16 pages, 3267 KiB  
Article
AI-Based Risk Score from Tumour-Infiltrating Lymphocyte Predicts Locoregional-Free Survival in Nasopharyngeal Carcinoma
by Made Satria Wibawa, Jia-Yu Zhou, Ruoyu Wang, Ying-Ying Huang, Zejiang Zhan, Xi Chen, Xing Lv, Lawrence S. Young and Nasir Rajpoot
Cancers 2023, 15(24), 5789; https://doi.org/10.3390/cancers15245789 - 10 Dec 2023
Cited by 2 | Viewed by 2418
Abstract
Background: Locoregional recurrence of nasopharyngeal carcinoma (NPC) occurs in 10% to 50% of cases following primary treatment. However, the current main prognostic markers for NPC, both stage and plasma Epstein–Barr virus DNA, are not sensitive to locoregional recurrence. Methods: We gathered 385 whole-slide [...] Read more.
Background: Locoregional recurrence of nasopharyngeal carcinoma (NPC) occurs in 10% to 50% of cases following primary treatment. However, the current main prognostic markers for NPC, both stage and plasma Epstein–Barr virus DNA, are not sensitive to locoregional recurrence. Methods: We gathered 385 whole-slide images (WSIs) from haematoxylin and eosin (H&E)-stained NPC sections (n = 367 cases), which were collected from Sun Yat-sen University Cancer Centre. We developed a deep learning algorithm to detect tumour nuclei and lymphocyte nuclei in WSIs, followed by density-based clustering to quantify the tumour-infiltrating lymphocytes (TILs) into 12 scores. The Random Survival Forest model was then trained on the TILs to generate risk score. Results: Based on Kaplan–Meier analysis, the proposed methods were able to stratify low- and high-risk NPC cases in a validation set of locoregional recurrence with a statically significant result (p < 0.001). This finding was also found in distant metastasis-free survival (p < 0.001), progression-free survival (p < 0.001), and regional recurrence-free survival (p < 0.05). Furthermore, in both univariate analysis (HR: 1.58, CI: 1.13–2.19, p < 0.05) and multivariate analysis (HR:1.59, CI: 1.11–2.28, p < 0.05), we also found that our methods demonstrated a strong prognostic value for locoregional recurrence. Conclusion: The proposed novel digital markers could potentially be utilised to assist treatment decisions in cases of NPC. Full article
(This article belongs to the Special Issue New Therapies and Immunological Findings in Nasopharyngeal Carcinoma)
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Review

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20 pages, 1518 KiB  
Review
The Role of Natural Killer Cells in the Tumor Immune Microenvironment of EBV-Associated Nasopharyngeal Carcinoma
by Shuzhan Li, Wei Dai, Ngar-Woon Kam, Jiali Zhang, Victor H. F. Lee, Xiubao Ren and Dora Lai-Wan Kwong
Cancers 2024, 16(7), 1312; https://doi.org/10.3390/cancers16071312 - 28 Mar 2024
Cited by 4 | Viewed by 2710
Abstract
Endemic nasopharyngeal carcinoma (NPC) is closely associated with the Epstein–Barr virus (EBV), which contributes to tumor development and influences the tumor immune microenvironment (TIME) in NPC. Natural killer (NK) cells, as part of the innate immune system, play a crucial role in responding [...] Read more.
Endemic nasopharyngeal carcinoma (NPC) is closely associated with the Epstein–Barr virus (EBV), which contributes to tumor development and influences the tumor immune microenvironment (TIME) in NPC. Natural killer (NK) cells, as part of the innate immune system, play a crucial role in responding to viral infections and malignant cell transformations. Notably, NK cells possess a unique ability to target tumor cells independent of major histocompatibility complex class I (MHC I) expression. This means that MHC I-deficient tumor cells, which can escape from effective T cell attack, are susceptible to NK-cell-mediated killing. The activation of NK cells is determined by the signals generated through inhibitory and activating receptors expressed on their surface. Understanding the role of NK cells in the complex TIME of EBV+ NPC is of utmost importance. In this review, we provide a comprehensive summary of the current understanding of NK cells in NPC, focusing on their subpopulations, interactions, and cytotoxicity within the TIME. Moreover, we discuss the potential translational therapeutic applications of NK cells in NPC. This review aims to enhance our knowledge of the role of NK cells in NPC and provide valuable insights for future investigations. Full article
(This article belongs to the Special Issue New Therapies and Immunological Findings in Nasopharyngeal Carcinoma)
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