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Skewed T-helper (Th)1/2- and Th17/T regulatory‑cell balances in patients with renal cell carcinoma.

Li L, Yang C, Zhao Z, Xu B, Zheng M, Zhang C, Min Z, Guo J, Rong R - Mol Med Rep (2014)

Bottom Line: Compared with healthy volunteers, a significant decrease in the peripheral percentages of Th1, activated and naïve Treg cells was observed in patients with RCC, while those of the Th2 and Th17 cells were increased.In particular, as the tumor stage and grade progressed, the levels of Th1, activated and naïve Treg cells in the peripheral blood decreased; however, the levels of Th2 and Th17 cells increased.Therefore, dysfunctional host anti‑tumor immunity was observed in patients with RCC, with a skewed Th1/Th2 and Th17/Treg balance.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.

ABSTRACT
The characterization of CD4+ T-cell subsets reflects the immune status and is important in the maintenance of tumorigenesis and homeostasis. To identify changes in the balance of T helper (Th)1, Th2, Th17 and regulatory T cells (Treg) in individuals with renal cell carcinoma (RCC), the present study investigated a total of 131 patients with RCC and 36 healthy volunteers. The number of CD4+ T‑bet+ cells, CD4+ GATA binding protein 3+ cells, CD4+ RAR-related orphan receptor γt+ cells, CD4+ CD25hi CD127lo CD45RA‑ cells and CD4+ CD25hi CD127lo CD45RA+ cells, defined as Th1, Th2, Th17, activated and naïve Treg cells, respectively, were detected in the peripheral blood using flow cytometric analysis. In addition, tumor‑infiltrating forkhead box P3 (Foxp3)+ cells were examined using immunohistochemistry. Compared with healthy volunteers, a significant decrease in the peripheral percentages of Th1, activated and naïve Treg cells was observed in patients with RCC, while those of the Th2 and Th17 cells were increased. In particular, as the tumor stage and grade progressed, the levels of Th1, activated and naïve Treg cells in the peripheral blood decreased; however, the levels of Th2 and Th17 cells increased. Furthermore, the number of tumor-infiltrating Foxp3+ cells increased with increasing tumor stage. These results demonstrated that the balance of Th1 and Th2 cells was skewed towards the Th2 profile and the balance of Th17 and Treg cells was skewed towards the Th17 profile in the peripheral blood of patients with renal cell carcinoma (RCC) and Treg cells were recruited to the tumor sites. Therefore, dysfunctional host anti‑tumor immunity was observed in patients with RCC, with a skewed Th1/Th2 and Th17/Treg balance.

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Proportion of Th1/Th2/Th17/Treg cells in different grades of RCC. (A) Proportion of activated Treg (CD4+ CD25+ CD127lo) cells reduced significantly in grades I-III of RCC compared with healthy volunteers. Furthermore, it reduced with increased grade and the proportion in grade III was significantly lower than in grade I. The percentages of (B) naïve Treg (CD4+ CD25+ CD127lo CD45A+) and (C) Th1 (CD4+ T-bet+) cells in grades I-III were also decreased and (C) the percentage of Th1 cells in grades II and III was significantly lower than that in grade I. (D and E) Percentages of Th2 (CD4+ GATA-3+) and Th17 (CD4+ RORγt+) cells in grades I-III were increased significantly compared with the healthy volunteers. (E) Percentage of Th17 cells was also increased in grade III compared with grade I. Data are expressed as the mean ± standard error of the mean. RCC, renal cell carcinoma; PBMC, peripheral blood mononuclear cell; Th, T helper cell; Treg, regulatory T cell; GATA3, GATA binding protein 3; RORγt, RAR-related orphan receptor γt. *P<0.05; **P<0.01; ***P<0.001.
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f3-mmr-11-02-0947: Proportion of Th1/Th2/Th17/Treg cells in different grades of RCC. (A) Proportion of activated Treg (CD4+ CD25+ CD127lo) cells reduced significantly in grades I-III of RCC compared with healthy volunteers. Furthermore, it reduced with increased grade and the proportion in grade III was significantly lower than in grade I. The percentages of (B) naïve Treg (CD4+ CD25+ CD127lo CD45A+) and (C) Th1 (CD4+ T-bet+) cells in grades I-III were also decreased and (C) the percentage of Th1 cells in grades II and III was significantly lower than that in grade I. (D and E) Percentages of Th2 (CD4+ GATA-3+) and Th17 (CD4+ RORγt+) cells in grades I-III were increased significantly compared with the healthy volunteers. (E) Percentage of Th17 cells was also increased in grade III compared with grade I. Data are expressed as the mean ± standard error of the mean. RCC, renal cell carcinoma; PBMC, peripheral blood mononuclear cell; Th, T helper cell; Treg, regulatory T cell; GATA3, GATA binding protein 3; RORγt, RAR-related orphan receptor γt. *P<0.05; **P<0.01; ***P<0.001.

Mentions: The proportion of activated Treg cells was reduced significantly in PMBCs of grade I-III RCC patients compared with that in healthy volunteers (grade II and III, P<0.0001; grade I, P<0.05). Furthermore, this proportion was reduced as the grade increased and the proportion in grade III patients was significantly lower than that in grade I patients (Fig. 3A). Similarly, the percentage of naïve Treg and Th1 cells in grades I-III was also decreased (P<0.0001; Fig. 3B and C). In addition, the percentage of Th1 cells in grades II and III was significantly lower than that in grade I (P<0.01 and P<0.05, respectively; Fig. 3C). However, the percentage of Th2 and Th17 cells in grades I-III was increased significantly compared with that in healthy volunteers (P<0.0001; Fig. 3D and E). The percentage of Th17 cells was also increased in grade III patients compared with that in grade I patients (Fig. 3E).


Skewed T-helper (Th)1/2- and Th17/T regulatory‑cell balances in patients with renal cell carcinoma.

Li L, Yang C, Zhao Z, Xu B, Zheng M, Zhang C, Min Z, Guo J, Rong R - Mol Med Rep (2014)

Proportion of Th1/Th2/Th17/Treg cells in different grades of RCC. (A) Proportion of activated Treg (CD4+ CD25+ CD127lo) cells reduced significantly in grades I-III of RCC compared with healthy volunteers. Furthermore, it reduced with increased grade and the proportion in grade III was significantly lower than in grade I. The percentages of (B) naïve Treg (CD4+ CD25+ CD127lo CD45A+) and (C) Th1 (CD4+ T-bet+) cells in grades I-III were also decreased and (C) the percentage of Th1 cells in grades II and III was significantly lower than that in grade I. (D and E) Percentages of Th2 (CD4+ GATA-3+) and Th17 (CD4+ RORγt+) cells in grades I-III were increased significantly compared with the healthy volunteers. (E) Percentage of Th17 cells was also increased in grade III compared with grade I. Data are expressed as the mean ± standard error of the mean. RCC, renal cell carcinoma; PBMC, peripheral blood mononuclear cell; Th, T helper cell; Treg, regulatory T cell; GATA3, GATA binding protein 3; RORγt, RAR-related orphan receptor γt. *P<0.05; **P<0.01; ***P<0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262517&req=5

f3-mmr-11-02-0947: Proportion of Th1/Th2/Th17/Treg cells in different grades of RCC. (A) Proportion of activated Treg (CD4+ CD25+ CD127lo) cells reduced significantly in grades I-III of RCC compared with healthy volunteers. Furthermore, it reduced with increased grade and the proportion in grade III was significantly lower than in grade I. The percentages of (B) naïve Treg (CD4+ CD25+ CD127lo CD45A+) and (C) Th1 (CD4+ T-bet+) cells in grades I-III were also decreased and (C) the percentage of Th1 cells in grades II and III was significantly lower than that in grade I. (D and E) Percentages of Th2 (CD4+ GATA-3+) and Th17 (CD4+ RORγt+) cells in grades I-III were increased significantly compared with the healthy volunteers. (E) Percentage of Th17 cells was also increased in grade III compared with grade I. Data are expressed as the mean ± standard error of the mean. RCC, renal cell carcinoma; PBMC, peripheral blood mononuclear cell; Th, T helper cell; Treg, regulatory T cell; GATA3, GATA binding protein 3; RORγt, RAR-related orphan receptor γt. *P<0.05; **P<0.01; ***P<0.001.
Mentions: The proportion of activated Treg cells was reduced significantly in PMBCs of grade I-III RCC patients compared with that in healthy volunteers (grade II and III, P<0.0001; grade I, P<0.05). Furthermore, this proportion was reduced as the grade increased and the proportion in grade III patients was significantly lower than that in grade I patients (Fig. 3A). Similarly, the percentage of naïve Treg and Th1 cells in grades I-III was also decreased (P<0.0001; Fig. 3B and C). In addition, the percentage of Th1 cells in grades II and III was significantly lower than that in grade I (P<0.01 and P<0.05, respectively; Fig. 3C). However, the percentage of Th2 and Th17 cells in grades I-III was increased significantly compared with that in healthy volunteers (P<0.0001; Fig. 3D and E). The percentage of Th17 cells was also increased in grade III patients compared with that in grade I patients (Fig. 3E).

Bottom Line: Compared with healthy volunteers, a significant decrease in the peripheral percentages of Th1, activated and naïve Treg cells was observed in patients with RCC, while those of the Th2 and Th17 cells were increased.In particular, as the tumor stage and grade progressed, the levels of Th1, activated and naïve Treg cells in the peripheral blood decreased; however, the levels of Th2 and Th17 cells increased.Therefore, dysfunctional host anti‑tumor immunity was observed in patients with RCC, with a skewed Th1/Th2 and Th17/Treg balance.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.

ABSTRACT
The characterization of CD4+ T-cell subsets reflects the immune status and is important in the maintenance of tumorigenesis and homeostasis. To identify changes in the balance of T helper (Th)1, Th2, Th17 and regulatory T cells (Treg) in individuals with renal cell carcinoma (RCC), the present study investigated a total of 131 patients with RCC and 36 healthy volunteers. The number of CD4+ T‑bet+ cells, CD4+ GATA binding protein 3+ cells, CD4+ RAR-related orphan receptor γt+ cells, CD4+ CD25hi CD127lo CD45RA‑ cells and CD4+ CD25hi CD127lo CD45RA+ cells, defined as Th1, Th2, Th17, activated and naïve Treg cells, respectively, were detected in the peripheral blood using flow cytometric analysis. In addition, tumor‑infiltrating forkhead box P3 (Foxp3)+ cells were examined using immunohistochemistry. Compared with healthy volunteers, a significant decrease in the peripheral percentages of Th1, activated and naïve Treg cells was observed in patients with RCC, while those of the Th2 and Th17 cells were increased. In particular, as the tumor stage and grade progressed, the levels of Th1, activated and naïve Treg cells in the peripheral blood decreased; however, the levels of Th2 and Th17 cells increased. Furthermore, the number of tumor-infiltrating Foxp3+ cells increased with increasing tumor stage. These results demonstrated that the balance of Th1 and Th2 cells was skewed towards the Th2 profile and the balance of Th17 and Treg cells was skewed towards the Th17 profile in the peripheral blood of patients with renal cell carcinoma (RCC) and Treg cells were recruited to the tumor sites. Therefore, dysfunctional host anti‑tumor immunity was observed in patients with RCC, with a skewed Th1/Th2 and Th17/Treg balance.

Show MeSH
Related in: MedlinePlus