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

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.

• Authors: Pierpaolo Correale, Maria Saveria Rotundo, Maria Teresa Del Vecchio, Cinzia Remondo, Cristina Migali, Chiara Ginanneschi, Kwong Y Tsang, Antonella Licchetta, Susanna Mannucci, Lucia Loiacono, Pierfrancesco Tassone, Guido Francini, Pierosandro Tagliaferri
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) Vol. 33 Issue 4 Pg. 435-41 (May 2010) ISSN: 1537-4513 [Electronic] United States
• PMID: 20386463 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

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

Topics

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