A study of the immune infiltrate and patient outcomes in esophageal cancer

Carcinogenesis. 2021 Apr 17;42(3):395-404. doi: 10.1093/carcin/bgaa101.


Objectives: Cancer patient outcomes and selection for novel therapies are heavily influenced by the immune contexture of the tumor microenvironment. Esophageal cancer is associated with poor outcomes. In contrast to colorectal cancer, where the immunoscore is increasingly used in prognostic staging, little is known about the immune cell populations in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (SCC), and their clinical significance.

Methods: Tissue microarrays were constructed from resected tumor tissue of 72 EAC patients and 23 SCC patients. Immunohistochemical staining of CD3, CD8, CD56, CD68, CD45RO, CD69, IFN-γ, IL-10, IL-4, IL-17, TGF-β, FOXP3 and CD107a was performed. Positivity was examined in both the stromal and epithelial compartments. Statistical analysis was performed to identify differences in immune cell infiltration and functional phenotypes between cancer subtypes and tissue compartments.

Results: This study identified that esophageal tumors are enriched with CD45RO+ and CD8+ cells and such positivity is significantly higher in SCC compared with EAC. Furthermore, the expression of CD45RO positively correlates with that of CD8 within the tumors of both patient cohorts, suggesting a dominance of memory cytotoxic T cells. This is supported by strong positivity of degranulation marker CD107a in the stromal compartment of EAC and SCC tumors. Cytokine staining revealed a mixed pro- and anti-inflammatory profile within EAC tumors.

Conclusions: Esophageal tumors are enriched with memory cytotoxic T cells. Applying these measurements to a larger cohort will ascertain the clinical utility of assessing specific lymphocyte infiltrates in EAC and SCC tumors with regards to future immunotherapy use, patient prognosis and outcomes.

Keywords: CD8+ T cells; esophageal cancer; immune contexture; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / metabolism
  • Cell Degranulation / immunology
  • Diagnosis, Differential
  • Esophageal Neoplasms / diagnosis
  • Esophageal Neoplasms / immunology*
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / surgery
  • Esophageal Squamous Cell Carcinoma / diagnosis
  • Esophageal Squamous Cell Carcinoma / immunology*
  • Esophageal Squamous Cell Carcinoma / pathology
  • Esophageal Squamous Cell Carcinoma / surgery
  • Esophagectomy
  • Esophagus / immunology
  • Esophagus / pathology
  • Esophagus / surgery
  • Female
  • Humans
  • Immunologic Memory
  • Immunophenotyping
  • Leukocyte Common Antigens / analysis
  • Leukocyte Common Antigens / metabolism
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism*
  • Male
  • Middle Aged
  • Prognosis
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*
  • Tissue Array Analysis
  • Tumor Microenvironment / immunology


  • Biomarkers, Tumor
  • Leukocyte Common Antigens

Supplementary concepts

  • Adenocarcinoma Of Esophagus