title: 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.affiliation: Department Giorgio Segre of Pharmacology, Siena University School of Medicine, Italy.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Correale
authors.forename: Maria Saveria
authors.initials: MS
authors.lastname: Rotundo
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Del Vecchio
authors.forename: Cinzia
authors.initials: C
authors.lastname: Remondo
authors.forename: Cristina
authors.initials: C
authors.lastname: Migali
authors.forename: Chiara
authors.initials: C
authors.lastname: Ginanneschi
authors.forename: Kwong Y
authors.initials: KY
authors.lastname: Tsang
authors.forename: Antonella
authors.initials: A
authors.lastname: Licchetta
authors.forename: Susanna
authors.initials: S
authors.lastname: Mannucci
authors.forename: Lucia
authors.initials: L
authors.lastname: Loiacono
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.forename: Guido
authors.initials: G
authors.lastname: Francini
authors.forename: Pierosandro
authors.initials: P
authors.lastname: Tagliaferri
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D002955:Leucovorin / Q000627:therapeutic use; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D000077150:Oxaliplatin; D011379:Prognosis; D011994:Recombinant Proteins; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000093542:Gemcitabine
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D009944:Organoplatinum Compounds; D011994:Recombinant Proteins; D000077150:Oxaliplatin; D003841:Deoxycytidine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002955:Leucovorin; D005472:Fluorouracil; D000093542:Gemcitabine
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