Nasopharyngeal carcinoma: current views on the tumor microenvironment's impact on drug resistance and clinical outcomes

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 22, 2024

Abstract The incidence of nasopharyngeal carcinoma (NPC) exhibits significant variations across different ethnic groups and geographical regions, with Southeast Asia North Africa being endemic areas. Of note, Epstein-Barr virus (EBV) infection is closely associated almost all the undifferentiated NPC cases. Over past three decades, radiation therapy chemotherapy have formed cornerstone treatment. However, recent advancements in immunotherapy introduced a range promising approaches for managing NPC. In light these developments, it has become evident that deeper understanding tumor microenvironment (TME) crucial. TME serves dual function, acting as promoter tumorigenesis while also orchestrating immunosuppression, thereby facilitating cancer progression enabling immune evasion. Consequently, comprehensive comprehension its intricate involvement initiation, progression, metastasis imperative development effective anticancer drugs. Moreover, given complexity inter-patient heterogeneity, personalized treatment should be designed to maximize therapeutic efficacy circumvent drug resistance. This review aims provide an in-depth exploration within context EBV-induced NPC, particular emphasis on pivotal role regulating intercellular communication shaping responses. Additionally, offers concise summary resistance mechanisms potential strategies their reversal, specifically relation chemoradiation therapy, targeted immunotherapy. Furthermore, advances clinical trials pertaining are discussed.

Language: Английский

---

Recurrent/Metastatic Nasopharyngeal Carcinoma Treatment from Present to Future: Where Are We and Where Are We Heading?

Current Treatment Options in Oncology, Journal Year: 2023, Volume and Issue: 24(9), P. 1138 - 1166

Published: June 15, 2023

Nasopharyngeal carcinoma (NPC) is distinct in its anatomic location and biology from other epithelial head neck cancer (HNC). There are 3 WHO subtypes, which considers the presence of Epstein-Barr virus (EBV) histopathology features. Despite survival benefit obtained modern treatment modalities techniques specifically local locally advanced setting, a number patients with this disease will recur subsequently die distant metastasis, locoregional relapse, or both. In recurrent ideal therapy approach continues to be topic discussion current recommendations platinum-based combination chemotherapy. Phase III clinical trials led approval pembrolizumab nivolumab for squamous cell (HNSCC) excluded NPC. No immune checkpoint inhibitor therapy, date, has been approved by FDA treat NPC although National Comprehensive Cancer Network (NCCN) do include use these agents. Hence, remains major challenge options. challenging as it really different diseases, much research required determine best options sequencing those This article going address data date discuss ongoing EBV + - inoperable recurrent/metastatic patients.

Language: Английский

---

Neoadjuvant and adjuvant toripalimab for locoregionally advanced nasopharyngeal carcinoma: a randomised, single-centre, double-blind, placebo-controlled, phase 2 trial

The Lancet Oncology, Journal Year: 2024, Volume and Issue: 25(12), P. 1563 - 1575

Published: Nov. 7, 2024

Language: Английский

---

Predictive value of immunotherapy-induced inflammation indexes: dynamic changes in patients with nasopharyngeal carcinoma receiving immune checkpoint inhibitors

Annals of Medicine, Journal Year: 2023, Volume and Issue: 55(2)

Published: Dec. 8, 2023

Background Immune checkpoint inhibitors (ICIs) have achieved substantial advancements in clinical care. However, there is no strong evidence for identified biomarkers of ICIs NPC.

Language: Английский

---

LMP2-mRNA lipid nanoparticle sensitizes EBV-related tumors to anti-PD-1 therapy by reversing T cell exhaustion

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Sept. 8, 2023

Targeting EBV-proteins with mRNA vaccines is a promising way to treat EBV-related tumors like nasopharyngeal carcinoma (NPC). We assume that it may sensitize immune checkpoint inhibitors.We developed an LMP2-mRNA lipid nanoparticle (C2@mLMP2) can be delivered tumor-draining lymph nodes. C2@mLMP2 exhibited high transfection efficiency and lysosomal escape ability induced increased proportion of CD8 + central memory T cells effective in the spleen mice model. A strong synergistic anti-tumor effect combination αPD-1 was observed tumor-bearing mice. The mechanism identified associated reverse cell exhaustion tumor microenvironment. pathological analysis further proved safety vaccine combined therapy.This first study proving EBV-mRNA PD-1 inhibitors for tumors. This provides theoretical evidence clinical trials expand application scenario efficacy immunotherapy NPC.

Language: Английский

---

Development and validation of a nomogram to predicting the efficacy of PD-1/PD-L1 inhibitors in patients with nasopharyngeal carcinoma

Clinical & Translational Oncology, Journal Year: 2024, Volume and Issue: 26(10), P. 2601 - 2607

Published: May 6, 2024

With the treatment of nasopharyngeal carcinoma (NPC) by PD-1/PD-L1 inhibitors used widely in clinic, it becomes very necessary to anticipate whether patients would benefit from it. We aimed develop a nomogram evaluate efficacy anti-PD-1/PD-L1 NPC patients.

Language: Английский

---

Incorporation of PD-1 blockade into induction chemotherapy improved tumor response in patients with locoregionally advanced nasopharyngeal carcinoma in a retrospective patient cohort

Oral Oncology, Journal Year: 2024, Volume and Issue: 154, P. 106867 - 106867

Published: May 25, 2024

Language: Английский

---

PD-L1 expression as a potential predictor of immune checkpoint inhibitor efficacy and survival in patients with recurrent or metastatic nasopharyngeal cancer: a systematic review and meta-analysis of prospective trials

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: June 3, 2024

Background The predictive value of programmed death-ligand 1 (PD-L1) expression in nasopharyngeal cancer (NPC) patients receiving immune checkpoint inhibitors (ICIs) remains controversial. This study aimed to evaluate the optimal threshold PD-L1 predicting efficacy ICIs with recurrent or metastatic (R/M) NPC. Methods A meta-analysis was performed by retrieving relevant literature from PubMed, EMBASE, and Cochrane Library databases. Data on pooled risk ratio (RR), mean overall survival (OS), progression-free (PFS), response rate (ORR) 95% confidence interval, 1%, 10%, 25% cutoff points were obtained examine role as a biomarker R/M NPC immunotherapy. Results In total, 1,312 14 studies included. An improvement PFS observed both ≥ 1% (RR = 0.76, CI 0.62–0.92, P 0.005) those < 0.68, CI: 0.35–1.32, 0.26) who received first-line treatment immunotherapy, no significant difference between these subgroups. ORR significantly higher (ORR 0.37) than 0.22) (P 0.01) undergoing subsequent-line treatment. However, when we used values 10% 25%, there positive (PD-L1 value) negative also tended be associated better OS. Conclusions Our suggested that immunotherapy could improve patients, regardless levels. Positive (≥ 1%) might potential for setting. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024495841 PROSPERO, identifier CRD42024495841.

Language: Английский

---

Metastatic sites of baseline as predictors in recurrent or metastatic nasopharyngeal carinoma treated with PD-L1 inhibitor: a secondary analysis of multicenter, single-arm, phase II study (KL-A167)

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(2)

Published: Jan. 3, 2025

Immune checkpoint inhibitors (ICIs) show optimal treatment effects on recurrent or metastatic nasopharyngeal carcinoma(R/M NPC). Nonetheless, whether sites impact ICIs efficacy remains unclear. We performed a secondary analysis of R/M NPC patients treated with KL-A167, programmed cell death-ligand 1(PD-L1) inhibitor, based multicenter, single-arm, phase II study from China between 2019 and 2021 years, which represents the first most comprehensive effectiveness PD-L1 inhibitor in who have been previously treated. The Cox proportional hazard model was utilized to evaluate association PFS OS. Sensitivity subgroup were carried out confirm reliability our findings. A total 153 included. mean age 47 years 81% males. All had distant metastasis, majority (n = 69) presenting more than 2 metastasis upon admission. collected included liver, lung, lymph bone. Among patients, 37.9% (58 patients) received anti-PD-L1 for minimum 6 months, 17.6% (27 at least 12 months. By conducting multivariate analysis, non-liver metastases presented significantly longer progress-free survival (PFS, HR:1.67, CI:1.09–0.2.55, p 0.018) overall (OS, HR:2.52, CI:1.49–4.28, < 0.001) compared those liver metastasis. median (72 vs. 144 days, 0.0001) OS (730 305 metastases. However, bone node no statistical significance (p > 0.005). Our sensitive showed less other site (0 1) shorter metastases(≥ 2). Furthermore, indicated robustness evidence indeed valuable prognostic factor survival. Compared sites, poor patterns when receiving therapy. provides rational urgent need explore modalities

Language: Английский

---

PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in nasopharyngeal carcinoma

Journal of Pathology and Translational Medicine, Journal Year: 2025, Volume and Issue: 59(1), P. 68 - 83

Published: Jan. 15, 2025

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, nasal epithelium clone (PLUNC) inhibit the growth NPC cells enhance cellular apoptosis differentiation. Currently, relationship between PLUNC (as a tumor-suppressor) PD-L1 in unclear.Methods: We collected clinical samples to verify PD-L1. plasmid was transfected into cells, variation verified western blot immunofluorescence. In we PD-L1, activating transcription factor 3 (ATF3), β-catenin Later, further that regulates through β-catenin. Finally, effect on co-immunoprecipitation (Co-IP).Results: found lower tissues than paracancer tissues. opposite PLUNC. Western immunofluorescence showed could upregulate ATF3 while downregulate ATF3/PD-L1 inhibiting inhibits entry nucleus. Co-IP experiments demonstrated inhibited interaction DEAD-box helicase 17 (DDX17) β-catenin.Conclusions: downregulates DDX17/β-catenin NPC.

Language: Английский

---