LAP+CD4+ T Cells Are Suppressors Accumulated in the Tumor Sites and Associated with the Progression of Colorectal Cancer

Purpose: Suppressor T cells are one of the determinants of colorectal cancer (CRC) clinical outcome. LAP(+)CD4(+) T cell is a recently identified subset of suppressor T cells. This study was designed to investigate their clinical relevance in patients with CRC. Experimental Design: Sixty patients with CRC and 24 healthy donors (HD) were enrolled in this study. The percentages of LAP(+)CD4(+) T cells in peripheral blood and tumor tissue were measured. The phenotype and functional relevance of LAP(+)CD4(+) T cells were analyzed subsequently. Results: The percentages of LAP(+)CD4(+) T cells in peripheral blood of patients with CRC were significantly higher than HD (HD vs. CRC: 3.1% +/- 0.78% vs. 8.8% +/- 5.8%, P < 0.0001) and in tumor tissue when compared with nontumor tissue (nontumor vs. tumor: 3.2% +/- 1.1% vs. 9.5% +/- 5.5%, P = 0.0002). In addition, LAP+CD4+ T cells with effector memory (EM) phenotype were more likely to accumulate in the tumor sites than in peripheral blood. These LAP(+)CD4(+) T cells produced significantly higher levels of IFN-gamma, IL-17 and comparatively lower IL-2 and very few IL-10. LAP(+)CD4(+) T cells could suppress the proliferation of LAP(-)CD4(+) T cells that were partially mediated by TGF-beta. Furthermore, these LAP(+)CD4(+) T cells accumulated in tumor site and increased further in the peripheral blood in patients with metastasis. Conclusions: LAP(+)CD4(+) T cells as a suppressor subset could accumulate in the tumor microenvironment and circulated more in the peripheral blood with tumor progression in patients with CRC. Clin Cancer Res; 18(19); 5224-33. (C)2012 AACR.