The intra-class heterogeneity of immunophenotyping and immune landscape in oesophageal cancer and clinical implications

Ann Med. 2021 Dec;53(1):626-638. doi: 10.1080/07853890.2021.1912385.

Abstract

Background: The response rate and survival benefit of immunotherapy vary among patients, implying specific immune status of an individual could be associated with the effect of immunotherapy. However, in-depth studies of immune subtypes (ISs), immune landscape and tumour microenvironment of oesophageal cancer (ESCA) and their clinical implications are less reported.

Methods: We first accessed data from publicly available databases and preprocessed it based on a standard protocol. Then, ISs were identified by unsupervised learning. Thereafter, the association of these ISs and tumour mutation burden (TMB), biomarkers of chemotherapy-induced immune response, tumour markers were also assessed. In addition, the immune characteristics, immune landscape, co-expression network of immune genes, and clinical implications were visualized and analysed.

Results: We identified three immunoclusters based on immune-associated genes with intra-class heterogeneity and prognostic value. Cluster-specific associations with TMB, markers of chemotherapy-induced immune response, and tumour markers were revealed. A 4-gene signature (risk score= -0.16514291×BHLHE22-0.03964046×MXRA8-0.15242778×SLIT2-0.05553572×SPON1) based on co-expressed genes in the immunoclusters was developed and externally validated.

Conclusions: In summary, we identified clinically relevant immunoclusters in both adenocarcinoma and squamous cell carcinoma of oesophagus, revealing the necessity of assessing the complexity and diversity of immune microenvironment for cancer immunotherapy.

Keywords: Immunophenotyping; immune landscape; immunotherapy; oesophageal cancer tumour microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / immunology*
  • Adenocarcinoma / mortality
  • Antineoplastic Agents, Immunological / therapeutic use
  • Biomarkers, Tumor / immunology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / mortality
  • Cluster Analysis
  • Databases, Factual
  • Drug Monitoring
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / immunology*
  • Esophageal Neoplasms / mortality
  • Genetic Heterogeneity*
  • Humans
  • Immunophenotyping
  • Immunotherapy
  • Predictive Value of Tests
  • Prognosis
  • Survival Analysis
  • Tumor Microenvironment / immunology*

Substances

  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor

Supplementary concepts

  • Adenocarcinoma Of Esophagus

Grants and funding

The work is supported by the Science and Technology Project of Guangdong Esophageal Cancer Institute [M201914] and Guangdong Province Science and Technology Special Fund [2020S00061].