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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 stages of RCC. (A) The percentage of activated Treg (CD4+ CD25+ CD127lo) cells was significantly decreased in stages I-IV (tumor-node-metastasis staging) of RCC patients compared with the healthy volunteers. (B) Percentage of activated Treg cells in stage III was decreased compared with that in stage I. The percentage of naïve Treg (CD4+ CD25+ CD127lo CD45A+) cells in stages I-IV of RCC patients was also decreased. (C) Percentage of Th1 (CD4+ T-bet+) cells in stage III was decreased significantly compared with in stage I and in the healthy volunteers. (D) Percentage of Th2 (CD4+ GATA-3+) cells was partially increased in stages I-IV compared with the healthy volunteers, although not significantly. (E) Percentages of Th17 (CD4+ RORγt+) cells in stages III and IV were markedly increased compared with that in the healthy volunteers. In addition, the proportion of Th17 cells in stages III and IV were higher compared with that in stage 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, T regulatory cell; RORγt, RAR-related orphan receptor γt; GATA3, GATA binding protein 3. *P<0.05; **P<0.01; ***P<0.001.
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f2-mmr-11-02-0947: Proportion of Th1/Th2/Th17/Treg cells in different stages of RCC. (A) The percentage of activated Treg (CD4+ CD25+ CD127lo) cells was significantly decreased in stages I-IV (tumor-node-metastasis staging) of RCC patients compared with the healthy volunteers. (B) Percentage of activated Treg cells in stage III was decreased compared with that in stage I. The percentage of naïve Treg (CD4+ CD25+ CD127lo CD45A+) cells in stages I-IV of RCC patients was also decreased. (C) Percentage of Th1 (CD4+ T-bet+) cells in stage III was decreased significantly compared with in stage I and in the healthy volunteers. (D) Percentage of Th2 (CD4+ GATA-3+) cells was partially increased in stages I-IV compared with the healthy volunteers, although not significantly. (E) Percentages of Th17 (CD4+ RORγt+) cells in stages III and IV were markedly increased compared with that in the healthy volunteers. In addition, the proportion of Th17 cells in stages III and IV were higher compared with that in stage 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, T regulatory cell; RORγt, RAR-related orphan receptor γt; GATA3, GATA binding protein 3. *P<0.05; **P<0.01; ***P<0.001.

Mentions: The percentage of activated Treg cells was significantly decreased in PMBCs of stage I-IV RCC patients compared with that in healthy volunteers (P<0.0001). In addition, the percentage of activated Treg cells in PMBCs of stage III RCC patients was lower than that in stage I patients (P<0.05; Fig. 2A). The percentage of naïve Treg cells in PMBCs of patients with stage I-IV RCC was also decreased (P<0.0001, Fig. 2B). The percentage of Th1 cells in PMBCs of stage III patients was significantly decreased compared with that in stage I patients and healthy volunteers (P<0.05; Fig. 2C). However, the percentage of Th2 cells was marginally increased in stage I-IV RCC patients compared with that in healthy volunteers, but no significant differences were observed (Fig. 2D). The percentage of Th17 cells in stage III and IV patients was markedly increased compared with that in healthy volunteers (stage III, P<0.0001; stage IV, P=0.0001; Fig. 2E). In addition, the proportion of Th17 cells in stage III and IV patients was higher than that in stage I patients (stage III, P=0.008; stage IV, P=0.002).


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 stages of RCC. (A) The percentage of activated Treg (CD4+ CD25+ CD127lo) cells was significantly decreased in stages I-IV (tumor-node-metastasis staging) of RCC patients compared with the healthy volunteers. (B) Percentage of activated Treg cells in stage III was decreased compared with that in stage I. The percentage of naïve Treg (CD4+ CD25+ CD127lo CD45A+) cells in stages I-IV of RCC patients was also decreased. (C) Percentage of Th1 (CD4+ T-bet+) cells in stage III was decreased significantly compared with in stage I and in the healthy volunteers. (D) Percentage of Th2 (CD4+ GATA-3+) cells was partially increased in stages I-IV compared with the healthy volunteers, although not significantly. (E) Percentages of Th17 (CD4+ RORγt+) cells in stages III and IV were markedly increased compared with that in the healthy volunteers. In addition, the proportion of Th17 cells in stages III and IV were higher compared with that in stage 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, T regulatory cell; RORγt, RAR-related orphan receptor γt; GATA3, GATA binding protein 3. *P<0.05; **P<0.01; ***P<0.001.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4262517&req=5

f2-mmr-11-02-0947: Proportion of Th1/Th2/Th17/Treg cells in different stages of RCC. (A) The percentage of activated Treg (CD4+ CD25+ CD127lo) cells was significantly decreased in stages I-IV (tumor-node-metastasis staging) of RCC patients compared with the healthy volunteers. (B) Percentage of activated Treg cells in stage III was decreased compared with that in stage I. The percentage of naïve Treg (CD4+ CD25+ CD127lo CD45A+) cells in stages I-IV of RCC patients was also decreased. (C) Percentage of Th1 (CD4+ T-bet+) cells in stage III was decreased significantly compared with in stage I and in the healthy volunteers. (D) Percentage of Th2 (CD4+ GATA-3+) cells was partially increased in stages I-IV compared with the healthy volunteers, although not significantly. (E) Percentages of Th17 (CD4+ RORγt+) cells in stages III and IV were markedly increased compared with that in the healthy volunteers. In addition, the proportion of Th17 cells in stages III and IV were higher compared with that in stage 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, T regulatory cell; RORγt, RAR-related orphan receptor γt; GATA3, GATA binding protein 3. *P<0.05; **P<0.01; ***P<0.001.
Mentions: The percentage of activated Treg cells was significantly decreased in PMBCs of stage I-IV RCC patients compared with that in healthy volunteers (P<0.0001). In addition, the percentage of activated Treg cells in PMBCs of stage III RCC patients was lower than that in stage I patients (P<0.05; Fig. 2A). The percentage of naïve Treg cells in PMBCs of patients with stage I-IV RCC was also decreased (P<0.0001, Fig. 2B). The percentage of Th1 cells in PMBCs of stage III patients was significantly decreased compared with that in stage I patients and healthy volunteers (P<0.05; Fig. 2C). However, the percentage of Th2 cells was marginally increased in stage I-IV RCC patients compared with that in healthy volunteers, but no significant differences were observed (Fig. 2D). The percentage of Th17 cells in stage III and IV patients was markedly increased compared with that in healthy volunteers (stage III, P<0.0001; stage IV, P=0.0001; Fig. 2E). In addition, the proportion of Th17 cells in stage III and IV patients was higher than that in stage I patients (stage III, P=0.008; stage IV, P=0.002).

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