Blimp-1+ regulatory T cells are associated with longer disease-free survival in colorectal cancer
KA Ward Hartstonge1, JL McCall3, AK Kamps1, T McCulloch1, E Cretney2, F Munro3, RA Kemp1.1Department of Microbiology and Immunology, University of Otago, New Zealand. 2Walter and Eliza Hall of Research Institute, Melbourne, Australia. 3Department of Surgical Sciences, University of Otago, New Zealand.
Analysis of tumour infiltrating immune cells in colorectal cancer is superior to the current staging at predicting disease-free survival. The Immunoscore has been proposed as a way to use CD3+ and CD8+ T cell infiltrates to stage disease; however T cell heterogeneity is not taken into account. Unlike in many cancers, a high frequency of tumour infiltrating FOXP3+ regulatory T cells (Tregs) are associated with good patient outcomes in colorectal cancer. Blimp-1+ Tregs are a population of T cells shown to be potently suppressive 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 early stage (II) colorectal cancer patients and to compare those with recurrent and non-recurrent disease (n=32). CD3 and CD8 were used for the Immunoscore. FOXP3, Blimp-1 and CD3 were used to quantify Blimp-1 regulatory T cells.
Patients with a high Immunoscore (high T cell infiltrate) had increased disease-free survival than patients with a low Immunoscore (low T cell infiltrate, Log-rank test p>0.001). The ability to predict patient outcome was improved by measuring the infiltrate of CD4+FOXP3+Blimp-1+ cells (Blimp-1+ Tregs, Log-rank test p>0.0001). Patients with a low Immunoscore but high infiltrate of CD4+FOXP3+Blimp-1+ cells at the invasive margin had increased disease-free survival than those with a low Immunoscore and a low infiltrate of CD4+FOXP3+Blimp-1+ cells.
These results indicate that Blimp-1+ Tregs may play an important role in patient outcome in colorectal cancer. Incorporation of Blimp-1+ Tregs into the Immunoscore may help to identify patients at high risk of recurrent disease. This may improve the staging and survival of colorectal cancer patients.
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