Impact of chemotherapy for colorectal cancer on regulatory T-cells and tumor immunity

Anticancer Res. 2011 Dec;31(12):4569-74.

Abstract

Background: Regulatory T-cells (Tregs) actively engage in the maintenance of immunological self-tolerance and immune homeostasis. The purpose of the present study was to determine how oxaliplatin plus infusional 5-fluorouracil and leucovorin (FOLFOX) and irinotecan plus infusional 5-fluorouracil and leucovorin (FOLFIRI) affect Tregs and other immune effectors.

Patients and methods: A total of 27 patients with metastatic colorectal cancer received the FOLFOX (n=17) or FOLFIRI (n=10) chemotherapeutic regimen. Blood samples were collected from patients before and 7 days after chemotherapy. The prevalence of Tregs co-expressing CD4(+)FoxP3(+) was analyzed with flow cytometry.

Results: The percentage and the number of CD4(+)FoxP3(+) Tregs were significantly reduced after FOLFOX and FOLFIRI in the patients who had high levels of Tregs before chemotherapy. On the other hand, the total number of lymphocytes and the population of CD4(+) T lymphocytes were unchanged.

Conclusion: FOLFOX and FOLFIRI may enhance antitumor immunity via suppression of Tregs.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • CD4-Positive T-Lymphocytes / immunology
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / immunology*
  • Female
  • Fluorouracil / administration & dosage
  • Forkhead Transcription Factors / biosynthesis
  • Humans
  • Immunotherapy / methods
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • T-Lymphocytes / immunology*

Substances

  • Antineoplastic Agents
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Leucovorin
  • Fluorouracil