[Phenotypic characteristics of LAP(+) CD4(+) T lymphocytes in colorectal cancer tissues].

Objective: To analyze the phenotypic characteristics of LAP(+) CD4(+) T lymphocytes and investigate their molecular mechanisms in colorectal cancer (CRC) microenvironment.

Methods: Fifty colorectal cancer patients treated in our two hospitals from January 2014 to May 2014 were included in this study. Their tumor tissues and adjacent normal tissues, peripheral blood samples, and peripheral blood samples of 25 healthy donors (HD) were collected to isolate the lymphocytes. The different expressions of CCR7, CD45RA, Foxp3, CTLA-4, CCR4 and CCR5 in LAP(+) CD4(+) T and LAP(-)CD4(+) T lymphocytes were analyzed by flow cytometry (FCM).

Results: The FCM assay detected that the percentage of LAP(+) CD4(+) T cells in peripheral blood of the CRC patients were significantly higher than that of HD [(9.44±3.18)% versus (1.49±1.00)%, P<0.001]. In addition, significantly more LAP(+) CD4(+) T cells were also recruited into tumor tissue than those in the tumor-adjacent normal tissue [(11.76±3.74)% versus (3.87±1.64)%, P<0.001]. LAP(+) CD4(+) T cells in the tumor-adjacent normal tissue and peripheral blood of both HDs and CRC patients mainly displayed a central memory phenotype. However, effector memory lymphocytes were predominant in the tumor tissue.In the tumor tissue, the expression of Foxp3 in the LAP(+) CD4(+) T cells was (3.87±1.12)%, significantly lower than that in the LAP(-)CD4(+) T cells (16.70±2.61)%, (P<0.001); the expression of CTLA-4 in the LAP(+) CD4(+) T cells was (36.36±19.14)%, significantly higher than the (19.60±8.91)% in the LAP(-)CD4(+) T cells (P<0.001); the expression of CCR4 in the LAP(+) CD4(+) T cells was (37.72±11.14)%, significantly higher than the (30.06±9.14)% in the LAP(-)CD4(+) T cells (P<0.001); and the expression of CCR5 in the LAP(+) CD4(+) T cells was (18.86±7.10)%, significantly higher than the (13.92±3.31)% in the LAP(-)CD4(+) T cells (P<0.001).

Conclusions: LAP(+) CD4(+) T cells with low expression of Foxp3 and high expressions of CTLA-4, CCR4 and CCR5 are tend to be enriched and accumulated in the tumor tissue. The unique phenotypic characteristics make these cells a distinct subset of lymphocytes, apparently different from the traditional CD4(+) CD25(+) Treg cells.