Regulatory (FoxP3+) T-cell tumor infiltration is a favorable prognostic factor in advanced colon cancer patients undergoing chemo or chemoimmunotherapy

J Immunother. 2010 May;33(4):435-41. doi: 10.1097/CJI.0b013e3181d32f01.

Abstract

Antitumor immune response and chemotherapy-induced immunomodulation in colon cancer patients represented the rationale to design new strategies, like GOLFIG chemoimmunotherapy (gemcitabine, oxaliplatin, 5-fluorouracil/folinic acid, granulocyte macrophage colony-stimulating factor, and aldesleukine), that resulted a safe and very active regimen. Antitumor activity and immunity feedback to GOLFIG were strictly correlated with the best outcome observed in patients with autoimmunity signs, increase of central memory T cells, and decrease of regulatory T cells (Treg) in the peripheral blood. We thus investigated a potential correlation between the Treg tumor infiltration at diagnosis and the clinical outcome in a current randomized phase 3 trial aimed to compare the GOLFIG regimen with the standard FOLFOX chemotherapy (GOLFIG-2). An immunohistochemistry study was carried out to quantify the infiltration of Treg/FoxP3+ T lymphocytes in tumor samples of 57 patients enrolled in the GOLFIG-2 trial. Treg tumor infiltration scores were correlated with overall survival, treatment-relative survival, and progression-free survival (PFS). Higher Treg tumor infiltration scores were associated with a better prognosis in the whole series (Treg high score vs. low score: overall survival=mean 43.2 mo vs. 28.6 mo, P=0.0005) and a better outcome after treatment (Treg high score vs. low score: PFS=mean 15.8 mo vs. 8.8 mo, P=0.0009; treatment-relative survival=mean 23.1 mo vs. 18.2 mo, P=0.004). PFS was significantly longer in GOLFIG high versus all other subgroups (mean 18.1 mo vs. 9.9 mo, P=0.01). Our results suggest that a higher FoxP3+ T-lymphocyte tumor infiltration score is a favorable prognostic factor in colon cancer patients undergoing chemo or chemoimmunotherapy.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma / diagnosis*
  • Carcinoma / immunology
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Carcinoma / physiopathology
  • Carcinoma / therapy
  • Colonic Neoplasms / diagnosis*
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / physiopathology
  • Colonic Neoplasms / therapy
  • Combined Modality Therapy
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease Progression
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / therapeutic use
  • Forkhead Transcription Factors / biosynthesis
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Humans
  • Immunohistochemistry
  • Immunotherapy*
  • Leucovorin / therapeutic use
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / therapeutic use
  • Oxaliplatin
  • Prognosis
  • Recombinant Proteins
  • Survival Analysis
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / pathology

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Organoplatinum Compounds
  • Recombinant Proteins
  • Oxaliplatin
  • Deoxycytidine
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • gemcitabine
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol