The immunological impact of neoadjuvant chemotherapy on the tumor microenvironment of esophageal squamous cell carcinoma

Ann Surg Oncol. 2012 May;19(5):1713-9. doi: 10.1245/s10434-011-1906-x. Epub 2011 Aug 6.

Abstract

Background: Esophageal cancer is an aggressive cancer with poor prognosis. However, little is known about the immune response in the tumor microenvironment after neoadjuvant chemotherapy.

Purpose: To investigate the immunological impact of neoadjuvant chemotherapy in the tumor microenvironment of esophageal squamous cell carcinoma.

Methods: Eighteen patients with esophageal squamous cell carcinoma with and without neoadjuvant chemotherapy were analyzed using immunohistochemical methods for human leukocyte antigen (HLA) class I heavy chain, CD4-, CD8-, and Foxp3-positive cell infiltration.

Results: The number of CD4 T cells in the stroma and within the cancer nest was significantly higher in the neoadjuvant chemotherapy group. The number of CD8 T cells in the stroma was significantly higher in the neoadjuvant chemotherapy group. HLA class I expression was more downregulated in the control group compared with the neoadjuvant chemotherapy group.

Conclusion: Neoadjuvant chemotherapy utilizing 5-fluorouracil and cisplatin in esophageal squamous cell carcinoma is useful to induce CD4 and CD8 T lymphocytes in the tumor microenvironment and to maintain HLA class I expression levels in combination with its direct cytotoxic effects.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • CD8-Positive T-Lymphocytes / immunology
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Chemotherapy, Adjuvant
  • Cisplatin / administration & dosage
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / immunology*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / surgery
  • Esophagectomy
  • Female
  • Fluorouracil / administration & dosage
  • Forkhead Transcription Factors / immunology
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Survival Rate
  • Tumor Microenvironment

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Histocompatibility Antigens Class I
  • Cisplatin
  • Fluorouracil