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

Mol Cancer. 2021 Jan 11;20(1):14. doi: 10.1186/s12943-020-01292-5.

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.

Keywords: Gene expression profiles; Immunotherapy responses; Nasopharyngeal carcinoma; Prognosis; Tumour microenvironment; Virtual microdissection.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Genetic Heterogeneity*
  • Genome, Human
  • Humans
  • Immunotherapy*
  • Nasopharyngeal Carcinoma / genetics
  • Nasopharyngeal Carcinoma / immunology*
  • Nasopharyngeal Carcinoma / therapy*
  • Prognosis
  • Reproducibility of Results
  • Tumor Microenvironment* / genetics