Role of LAP~+CD4~+ T cells in the tumor microenvironment of colorectal cancer

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:mj830115
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AIM To investigate the abundance and potential functions of LAP~+CD4~+ T cells in colorectal cancer(CRC). METHODS Proportions of LAP~+CD4~+ T cells were examined in peripheral blood and tumor/paratumor tissues of CRC patients and healthy controls using flow cytometry. Expression of phenotypic markers such as forkhead box(Fox)p3, cytotoxic T-lymphocyte-associated protein(CTLA)-4, chemokine CC receptor (CCR)4 and CCR5 was measured using flow cytometry. LAP~-CD4~+ and LAP~+CD4~+ T cells were isolated using a magnetic cellsorting system and cell purity was analyzed by flow cytometry. Real-time quantitative polymerase chain reaction was used to measure expression of cytokines interleukin (IL)-10 and transforming growth factor(TGF)-β.RESULTS The proportion of LAP~+CD4~+ T cells was significantly higher in peripheral blood from patients (9.44% ± 3.18%) than healthy controls (1.49% ± 1.00%, P < 0.001). Among patients, the proportion of LAP~+CD4~+ T cells was significantly higher in tumor tissues(11.76% ± 3.74%) compared with paratumor tissues (3.87% ± 1.64%, P < 0.001). We also observed positive correlations between the proportion of LAP~+CD4~+ T cells and TNM stage(P < 0.001), distant metastasis(P < 0.001) and serum level of carcinoembryonic antigen(P < 0.05). Magnetic-activated cell sorting gave an overall enrichment of LAP~+CD4~+ T cells (95.02% ± 2.87%), which was similar for LAP~-CD4~+ T cells(94.75% ± 2.76%). In contrast to LAP~-CD4~+ T cells, LAP~+CD4~+ T cells showed lower Foxp3 expression but significantly higher levels of CTLA-4, CCR4 and CCR5(P < 0.01). LAP~+CD4~+ T cells expressed significantly larger amounts of IL-10 and TGF-β but lower levels of IL-2, IL-4, IL-17 and interferon-γ, compared with LAPCD4+ T cells.CONCLUSION LAP~+CD4~+ T cells accumulated in the tumor microenvironment of CRC patients and were involved in immune evasion mediated by IL-10 and TGF-β. AIM To investigate the abundance and potential functions of LAP ~ + CD4 ~ + T cells in colorectal cancer (CRC). METHODS Proportions of LAP ~ + CD4 ~ + T cells were examined in peripheral blood and tumor / paratumor tissues of CRC patients and healthy controls using flow cytometry. Expression of phenotypic markers such as forkhead box (Fox) p3, cytotoxic T-lymphocyte-associated protein (CTLA) -4, chemokine CC receptor (CCR) 4 and CCR5 was measured using flow cytometry. LAP ~ -CD4 ~ + and LAP ~ + CD4 ~ + T cells were isolated using a magnetic cell typing system and cell purity was analyzed by flow cytometry. Real-time quantitative polymerase chain reaction was used to measure expression of cytokines interleukin (IL) -10 and transforming growth (TGF) -β.RESULTS The proportion of LAP ~ + CD4 ~ + T cells was significantly higher in peripheral blood from patients (9.44% ± 3.18%) than healthy controls (1.49% ± 1.00%, P <0.001) patients, the proportion of LAP ~ + CD4 ~ + T cells was significantly higher in tumor t (11.76% ± 3.74%) compared with paratumor tissues (3.87% ± 1.64%, P <0.001). We also observed positive correlations between the proportion of LAP ~ + CD4 ~ + T cells and TNM stage (P <0.001) and serum level of carcinoembryonic antigen (P <0.05). Magnetic-activated cell sorting gave an overall enrichment of LAP ~ + CD4 ~ + T cells (95.02% ± 2.87% ~ CD4 ~ + T cells showed lower Foxp3 expression but significantly higher levels of CTLA-4, CCR4 and T cells (94.75% ± 2.76% CCR5 (P <0.01). LAP ~ + CD4 ~ + T cells expressed significantly larger amounts of IL-10 and TGF-β but lower levels of IL-2, IL- T cells. CONCLUSION LAP ~ + CD4 ~ + T cells accumulated in the tumor microenvironment of CRC patients and were involved in immune evasion mediated by IL-10 and TGF-β.
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