CD4? T cells expressing latency-associated peptide and Foxp3 are an activated subgroup of regulatory T cells enriched in patients with colorectal cancer.

ABSTRACT: Latency-associated peptide (LAP) - expressing regulatory T cells (Tregs) are important for immunological self-tolerance and immune homeostasis. In order to investigate the role of LAP in human CD4?Foxp3? Tregs, we designed a cross-sectional study that involved 42 colorectal cancer (CRC) patients. The phenotypes, cytokine-release patterns, and suppressive ability of Tregs isolated from peripheral blood and tumor tissues were analyzed. We found that the population of LAP-positive CD4?Foxp3? Tregs significantly increased in peripheral blood and cancer tissues of CRC patients as compared to that in the peripheral blood and tissues of healthy subjects. Both LAP? and LAP? Tregs had a similar effector/memory phenotype. However, LAP? Tregs expressed more effector molecules, including tumor necrosis factor receptor II, granzyme B, perforin, Ki67, and CCR5, than their LAP? negative counterparts. The in vitro immunosuppressive activity of LAP? Tregs, exerted via a transforming growth factor-?-mediated mechanism, was more potent than that of LAP? Tregs. Furthermore, the enrichment of LAP? Treg population in peripheral blood mononuclear cells (PBMCs) of CRC patients correlated with cancer metastases. In conclusion, we found that LAP? Foxp3? CD4? Treg cells represented an activated subgroup of Tregs having more potent regulatory activity in CRC patients. The increased frequency of LAP? Tregs in PBMCs of CRC patients suggests their potential role in controlling immune response to cancer and presents LAP as a marker of tumor-specific Tregs in CRC patients.

SUBMITTER: Mahalingam J 

PROVIDER: S-EPMC4182495 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature