PD-L1 mediated immune escape in nasopharyngeal carcinoma: Impact of LMP1 and IFN-γ on immune surveillance
Year: 2024
Type: article
Abstract: Nasopharyngeal carcinoma (NPC) is a distinct malignancy in head and neck cancer, notably linked to Epstein-Barr virus (EBV) infections in regions with high prevalence. NPC's tumor microenvironment fosters immune escape mechanisms that support tumor cell survival, with programmed death-ligand 1 (PD-L1) as a key player. PD-L1 expression on NPC cells binds to the programmed death-1 (PD-1) receptor on T cells, thereby creating an immunosuppressive environment that impairs immune surveillance. Two significant modulators of PD-L1 expression in NPC include the EBV-encoded latent membrane protein 1 (LMP1) and the immune cytokine interferon-gamma (IFN-γ). Together, they contribute to the intricate regulation of PD-L1, enhancing immune evasion and complicating the landscape for effective treatment approaches. This review explores the molecular mechanisms underlying PD-L1 upregulation, focusing on LMP1's activation of the NF-κB and JAK/STAT pathways and IFN-γ′s paradoxical role in facilitating immune escape. Clinical evidence indicates that PD-L1 expression correlates with poor prognosis and resistance to standard therapies in NPC patients. Understanding these regulatory pathways may inform potential therapeutic strategies, including immune checkpoint inhibitors, combination therapies, and novel immune-based approaches tailored to NPC's unique etiology. By providing a comprehensive synthesis of existing studies, this review highlights the interplay between PD-L1, LMP1, and IFN-γ, offering a framework for innovative therapeutic strategies targeting immune escape mechanisms. Identifying patients most likely to benefit from immune-targeted approaches and leveraging combination treatments could improve outcomes for NPC patients facing advanced or resistant disease. • PD-L1 as a Key Mediator of Immune Evasion in Nasopharyngeal Carcinoma: PD-L1 facilitates immune escape in nasopharyngeal carcinoma by inhibiting immune responses, enabling tumor persistence. Targeting PD-L1 could enhance treatment outcomes by reactivating immune surveillance. • Influence of LMP1 and IFN-γ on PD-L1-Driven Immune Escape Mechanisms: LMP1 and IFN-γ upregulate PD-L1 expression in NPC, intensifying immune evasion. Understanding these interactions may uncover new therapeutic targets to counter immune resistance. • The Role of PD-L1 in Disrupting Immune Surveillance in Nasopharyngeal Carcinoma: Overexpression of PD-L1 in NPC interferes with immune detection, helping tumor cells evade immune attacks. This disruption fosters unchecked tumor growth and metastasis. • Exploring LMP1 and IFN-γ Contributions to Immune Escape in Nasopharyngeal Cancer: LMP1 and IFN-γ promote PD-L1 activity, weakening immune responses against NPC. Blocking these pathways could reduce immune escape and improve treatment efficacy in NPC.
Source: Oral Oncology Reports
Institutions: Chettinad Academy of Research and Education, Jazan University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,100
OpenAlex ID: W4404505933