Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses

Abstract

Currently, there is no strong evidence of the well-established biomarkers for immune checkpoint inhibitors (ICIs) in nasopharyngeal carcinoma (NPC). Here, we aimed to reveal the heterogeneity of tumour microenvironment (TME) through virtual microdissection of gene expression profiles. An immune-enriched subtype was identified in 38% (43/113) of patients, which was characterized by significant enrichment of immune cells or immune responses. The remaining patients were therefore classified as a non-Immune Subtype (non-IS), which exhibited highly proliferative features. Then we identified a tumour immune evasion state within the immune-enriched subtype (18/43, 42%), in which high expression of exclusion- and dysfunction-related signatures was observed. These subgroups were designated the Evaded and Active Immune Subtype (E-IS and A-IS), respectively. We further demonstrated that A-IS predicted favourable survival and improved ICI response as compared to E-IS and non-IS. In summary, this study introduces the novel immune subtypes and demonstrates their feasibility in tailoring immunotherapeutic strategies.

Influence of Epstein–Barr virus and human papillomavirus infection on macrophage migration inhibitory factor and macrophage polarization in nasopharyngeal carcinoma

“…Approximately 70% of patients with NPC are diagnosed at an advanced stage and are more prone to therapy failure due to radioresistance [ 2 ]. NPC is characterized by Epstein–Barr virus (EBV) infection and substantial lymphocyte infiltration [ 3 ], which consists of the immune microenvironment, indicating the importance of EBV and the tumor microenvironment in NPC pathogenesis. EBV infection is considered the most important etiological factor of NPC [ 4 ] and is reported to change the tumor microenvironment to benefit itself, particularly immune evasion [ 5 ].…”

Epstein–Barr Virus Epithelial Cancers—A Comprehensive Understanding to Drive Novel Therapies

“…Bulk transcriptomic and recently single-cell RNA sequencing (scRNA-seq) also revealed different cell populations and subtypes of TIME in NPC-broadly categorised into inflamed, hot, and immune excluded. A few studies have separately identified subtypes of NPC according to immune and nonimmune gene signatures, observing the immune gene signature-rich subtypes correlating with better survival outcomes (108,148). Chen et al described an immuneenriched stroma in 38% (43/113) of patients, characterised by significant enrichment of immune response signatures.…”

Multimodality Management of EBV-Associated Nasopharyngeal Carcinoma

“…Recent work has detected differences in TME between various types of NPC. Certain subsets of NPC have an immune-rich TME, comprising of high concentrations of host immune cells (T-cells, B-cells, macrophages) as well as increased expression of checkpoint inhibitor proteins such as programmed death ligand 1 (PD-L1) and transforming growth factor (TGF)-beta [ 24 , 25 , 26 ] ( Figure 1 ). It is hypothesized that these immune-rich NPCs may be associated with more favorable outcomes and are more readily targeted by new therapies such as immunotherapy.…”

“…It is hypothesized that these immune-rich NPCs may be associated with more favorable outcomes and are more readily targeted by new therapies such as immunotherapy. The reader is referred to the excellent review that was recently published on the topic and provides a comprehensive review of the complexity of the TME within NPC [ 24 ].…”