High-Dimensional Mass Cytometric Analysis Reveals an Increase in Effector Regulatory T Cells as a Distinguishing Feature of Colorectal Tumors

• Published in: The Journal of immunology (1950) 2019-03, Vol.202 (6), p.1871-1884
• Main Authors: Norton, Samuel E, Ward-Hartstonge, Kirsten A, McCall, John L, Leman, Julia K H, Taylor, Edward S, Munro, Fran, Black, Michael A, Fazekas de St Groth, Barbara, McGuire, Helen M, Kemp, Roslyn A
• Format: Article
• Language: English
• Subjects: Aged; Cell Separation - methods; Colorectal Neoplasms - immunology; Female; Humans; Lymphocyte Activation - immunology; Lymphocytes, Tumor-Infiltrating - immunology; Male; Middle Aged; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Regulatory - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1801368

T cell infiltration of tumors plays an important role in determining colorectal cancer disease progression and has been incorporated into the Immunoscore prognostic tool. In this study, mass cytometry was used to demonstrate a significant increase in the frequency of both conventional CD25 FOXP3 CD127 regulatory T cells (Tregs) as well as BLIMP-1 Tregs in the tumor compared with nontumor bowel (NTB) of the same patients. Network cluster analyses using SCAFFoLD, VorteX, and CITRUS revealed that an increase in BLIMP-1 Tregs was a single distinguishing feature of the tumor tissue compared with NTB. BLIMP-1 Tregs represented the most significantly enriched T cell population in the tumor compared with NTB. The enrichment of ICOS, CD45RO, PD-1, PDL-1, LAG-3, CTLA-4, and TIM-3 on BLIMP-1 Tregs suggests that BLIMP-1 Tregs have a more activated phenotype than conventional Tregs and may play a role in antitumor immune responses.