Immunotherapeutic approaches in nasopharyngeal carcinoma

Chow, J.C.H.; Ngan, Roger Kc; Cheung, Ka Man; Cho, William C.

doi:10.1080/14712598.2019.1650910

Cited by 45 publications

(38 citation statements)

References 68 publications

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“…Subtype III, with high expression of T effector genes and high IFNγ signature, may be enriched for potential responders to checkpoint blockade therapy . This review differs from previous articles by providing a comprehensive analysis of both current and future immunotherapy NPC trials …”

Section: Introductionmentioning

confidence: 95%

“…[12][13][14] The second group includes active immunotherapy approaches, by, for example, stimulation of tumour-specific immune responses through the delivery of APCs loaded with tumour antigens, or vaccination. [15][16][17][18] An alternative approach is an administration of cytotoxic cells (e.g. tumour infiltrating/ transgenic T lymphocytes and natural killers) which directly and preferentially target cancer cells.…”

Section: Current Treatmentsmentioning

confidence: 99%

“…26 This review differs from previous articles by providing a comprehensive analysis of both current and future immunotherapy NPC trials. 18,29…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

“…The second group includes active immunotherapy approaches, by, for example, stimulation of tumour‐specific immune responses through the delivery of APCs loaded with tumour antigens, or vaccination . An alternative approach is an administration of cytotoxic cells (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Masterson

Howard

Gonzalez-Cruz

et al. 2020

Intl Journal of Cancer

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Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on‐going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA‐4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first‐line treatment for metastatic NPC (PFS 68% at 1‐year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1‐year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non‐PD1 checkpoint inhibitors but 11 on‐going studies include alternative targets (e.g. PD‐L1/CTLA‐4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti‐PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.

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Section: Introductionmentioning

confidence: 95%

Section: Current Treatmentsmentioning

confidence: 99%

“…26 This review differs from previous articles by providing a comprehensive analysis of both current and future immunotherapy NPC trials. 18,29…”

Section: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Masterson

Howard

Gonzalez-Cruz

et al. 2020

Intl Journal of Cancer

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“…Programmed death ligand 1 (PD-L1) expression was also reported to be correlated with poor outcomes of NPC (38,39). Targeting the immune checkpoint pathway was an immunotherapeutic strategy for NPC (40). In this study, GO and KEGG analysis revealed that the risk model was significantly associated with immunerelated signal pathway.…”

Section: Discussionmentioning

confidence: 73%

Gene Signatures and Prognostic Values of m6A Genes in Nasopharyngeal Carcinoma

Xiao

et al. 2020

Front. Oncol.

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Nasopharyngeal carcinoma (NPC) is a malignant tumor with a high rate of local invasion and early distant metastasis. Accumulating studies suggest that N6-methyladenosine methylation (m 6 A) is closely related to tumorigenesis. However, the relationship between m 6 A-related genes and prognosis of NPC is poorly understood. Our research aims to discover the prognostic value of m 6 A RNA methylation genes in NPC. In this study, we analyzed the differentially expressed m 6 A-related genes between NPC samples and normal control samples and found that two upregulated genes (YTHDF3 and IGF2BP2) and one downregulated gene (METTL3) were overlapped in GSE68799 and GSE53819. Next, we found that high expression of IGF2BP1 and low expression of METTL3 and YTHDF3 in NPC patients showed poor progression-free survival (PFS). Subsequently, the four m 6 A genes were selected for consensus cluster analysis, and risk models were established. The risk signature, using three genes (GF2BP1 + IGF2BP2 + METTL3), was an independent prognostic factor and predicts the clinicopathological features of NPC. Additionally, the GO, KEGG analysis, and CIBERSORT algorithm revealed that the risk signature was closely associated to immune infiltration in NPC. Finally, the expression and clinical significance of METTL3 were successfully validated in NPC tissues using immunohistochemical techniques. In conclusion, our finding revealed the potential role of m 6 A modification in NPC, providing novel insight into NPC prognosis and therapeutic strategies.

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TMEM52B Isoforms P18 and P20 Differentially Promote the Oncogenesis and Metastasis of Nasopharyngeal Carcinoma

Zhu,

Lu,

et al. 2024

Advanced Science

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Transmembrane protein 52B (TMEM52B), a newly identified tumor‐related gene, has been reported to regulate various tumors, yet its role in nasopharyngeal carcinoma (NPC) remains unclear. Transcriptomic analysis of NPC cell lines reveals frequent overexpression of TMEM52B, and immunohistochemical results show that TMEM52B is associated with advanced tumor stage, recurrence, and decreased survival time. Depleting TMEM52B inhibits the proliferation, migration, invasion, and oncogenesis of NPC cells in vivo. TMEM52B encodes two isoforms, TMEM52B‐P18 and TMEM52B‐P20, differing in their N‐terminals. While both isoforms exhibit similar pro‐oncogenic roles and contribute to drug resistance in NPC, TMEM52B‐P20 differentially promotes metastasis. This functional discrepancy may be attributed to their distinct subcellular localization; TMEM52B‐P18 is confined to the cytoplasm, while TMEM52B‐P20 is found both at the cell membrane and in the cytoplasm. Mechanistically, cytoplasmic TMEM52B enhances AKT phosphorylation by interacting with phosphoglycerate kinase 1 (PGK1), fostering NPC growth and metastasis. Meanwhile, membrane‐localized TMEM52B‐P20 promotes E‐cadherin ubiquitination and degradation by facilitating its interaction with the E3 ubiquitin ligase NEDD4, further driving NPC metastasis. In conclusion, the TMEM52B‐P18 and TMEM52B‐P20 isoforms promote the metastasis of NPC cells through different mechanisms. Drugs targeting these TMEM52B isoforms may offer therapeutic benefits to cancer patients with varying degrees of metastasis.

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Immunotherapeutic approaches in nasopharyngeal carcinoma

Cited by 45 publications

References 68 publications

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Gene Signatures and Prognostic Values of m6A Genes in Nasopharyngeal Carcinoma

TMEM52B Isoforms P18 and P20 Differentially Promote the Oncogenesis and Metastasis of Nasopharyngeal Carcinoma

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