title: Inclusion of BLIMP-1+effector regulatory T cells improves the Immunoscore in a cohort of New Zealand colorectal cancer patients: a pilot study.
abstract: Analysis of tumour-infiltrating T cells in colorectal cancer can predict disease-free survival. The Immunoscore, obtained by quantifying tumour-infiltrating CD3+and CD8+T cells, may improve current staging. Effector regulatory T cells are a potently suppressive subset in mice and, while present in human colorectal cancer, their role in patient outcome is unknown. Immunofluorescence was used to analyse immune cell infiltrates in patients with early (stage II) colorectal cancer with (n = 13) and without (n = 19) recurrent disease. CD3 and CD8 were used for the Immunoscore; FOXP3, BLIMP-1 and CD3 to identify effector regulatory T cells. Patients with high Immunoscores had increased disease-free survival compared to patients with low Immunoscores (Log-rank test p < 0.01). Prediction of outcome was further improved by stratifying patients with a low Immunoscore according to CD3+FOXP3+BLIMP-1+cell infiltration at the invasive margin. Patients with a low Immunoscore and high infiltrate of CD3+FOXP3+BLIMP-1+cells tended to have better disease-free survival than patients with low Immunoscore and low infiltrate of CD3+FOXP3+BLIMP-1+cells. Patients with a high Immunoscore had better disease-free survival than patients with a low Immunoscore and low infiltrate of CD3+ FOXP3+ BLIMP-1+ cells (Log-rank test p < 0.001). These results indicate that tumour infiltration with effector regulatory T cells improves the prognostic value of the Immunoscore and implies that these cells may play a role in colorectal cancer patient outcome.
authors.affiliation: Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Ward-Hartstonge
authors.affiliation: Department of Surgical Sciences, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.
authors.forename: John L
authors.initials: JL
authors.lastname: McCall
authors.affiliation: Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: McCulloch
authors.affiliation: Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.
authors.forename: Ann-Kristin
authors.initials: AK
authors.lastname: Kamps
authors.affiliation: Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.
authors.forename: Adam
authors.initials: A
authors.lastname: Girardin
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.|Department of Medical Biology, The University of Melbourne, Parkville, VIC, 3052, Australia.
authors.forename: Erika
authors.initials: E
authors.lastname: Cretney
authors.affiliation: Department of Surgical Sciences, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.
authors.forename: Fran M
authors.initials: FM
authors.lastname: Munro
authors.affiliation: Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, 9054, New Zealand. roslyn.kemp@otago.ac.nz.
authors.forename: Roslyn A
authors.initials: RA
authors.lastname: Kemp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007159:Immunologic Tests; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009520:New Zealand; D010865:Pilot Projects; D000074462:Positive Regulatory Domain I-Binding Factor 1; D011237:Predictive Value of Tests; D011379:Prognosis; D012097:Repressor Proteins / Q000378:metabolism*; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012097:Repressor Proteins; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1
keywords: BLIMP-1; Colorectal neoplasms; Disease-free survival; Regulatory T lymphocytes; T lymphocytes