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Preferential recruitment of Th17 cells to cervical cancer via CCR6-CCL20 pathway.

Yu Q, Lou XM, He Y - PLoS ONE (2015)

Bottom Line: However, the source of the increased tumor-infiltrating Th17 cells remains poorly understood.We investigated the prevalence, phenotype and trafficking property of Th17 cells in patients with cervical cancer.In conclusion, Th17 cells are recruited into tumor tissues preferentially through CCR6-CCL20 pathway, which can serve as a novel therapeutic target for cervical cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Hangzhou Obstetrics and Gynecology Hospital, Hangzhou First People's Hospital, Hangzhou, China.

ABSTRACT
Our previous studies suggest that Th17 cells accumulate within tumor tissues and correlate with recurrence of cervical cancer patients. However, the source of the increased tumor-infiltrating Th17 cells remains poorly understood. We investigated the prevalence, phenotype and trafficking property of Th17 cells in patients with cervical cancer. Our results showed that Th17 cells highly aggregated within tumor tissues in an activated phenotype with markedly increased expression of CCR6. Correspondingly, level of CCL20 in the tumor tissues was significantly higher than that in non-tumor and normal control tissues, and strongly positively associated with Th17 cells. Further, in vitro migration assay showed CCL20 had effective chemotaxis to circulating Th17 cells. In conclusion, Th17 cells are recruited into tumor tissues preferentially through CCR6-CCL20 pathway, which can serve as a novel therapeutic target for cervical cancer.

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Th17 cells are highly enriched in tumors of patients with cervical cancer.Th17 cells were gated from CD3+ T cells by flow cytometry. (A) Representative IL-17 expression profiles in CD4+ T cells from the four studied groups. The percentages represent the frequency of Th17 cells among CD4+ T cells. (B) Statistical analysis show that the frequency of Th17 cells was higher in patients with cervical cancer, especially among tumor-infiltrating lymphocytes (n = 35). **P < 0.01, ***P < 0.001. (C) Representative images for Th17 cells (IL-17+) and Tregs (FoxP3+) infiltration in cervical cancer tissue from the same patient. Immunostained cells (brown, indicated by black arrow) and tumor cells (blue). Magnification,×100.
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pone.0120855.g001: Th17 cells are highly enriched in tumors of patients with cervical cancer.Th17 cells were gated from CD3+ T cells by flow cytometry. (A) Representative IL-17 expression profiles in CD4+ T cells from the four studied groups. The percentages represent the frequency of Th17 cells among CD4+ T cells. (B) Statistical analysis show that the frequency of Th17 cells was higher in patients with cervical cancer, especially among tumor-infiltrating lymphocytes (n = 35). **P < 0.01, ***P < 0.001. (C) Representative images for Th17 cells (IL-17+) and Tregs (FoxP3+) infiltration in cervical cancer tissue from the same patient. Immunostained cells (brown, indicated by black arrow) and tumor cells (blue). Magnification,×100.

Mentions: To study the distribution of Th17 cells at tumor site, NIL and TIL were isolated from paired nontumor and tumor tissues in 35 patients with cervical cancer and characterized via flow cytometry (Fig. 1A). As expected, the frequency of Th17 cells in tumor tissue, representing 11.49 ± 1.19% of CD4+ T cells, was significantly higher than those in non-tumor tissue (3.68 ± 0.48%, P < 0.001), and peripheral blood of patients with cervical cancer (4.96 ± 0.72%, P < 0.01) and healthy donors (1.67 ± 0.19%, P < 0.001; Fig. 1B). Additionally, the proportion of circulating Th17 cells was also higher in patients with cervical cancer compared with healthy donors (P < 0.001). Immunohistochemical staining also observed substantial Th17 cells in tumor tissue of cervical cancer, even higher than regulatory T cells (Tregs) in the same environment (Fig. 1C). These results collectively suggest that Th17 cells are highly enriched in patients with cervical cancer, especially in tumor tissue.


Preferential recruitment of Th17 cells to cervical cancer via CCR6-CCL20 pathway.

Yu Q, Lou XM, He Y - PLoS ONE (2015)

Th17 cells are highly enriched in tumors of patients with cervical cancer.Th17 cells were gated from CD3+ T cells by flow cytometry. (A) Representative IL-17 expression profiles in CD4+ T cells from the four studied groups. The percentages represent the frequency of Th17 cells among CD4+ T cells. (B) Statistical analysis show that the frequency of Th17 cells was higher in patients with cervical cancer, especially among tumor-infiltrating lymphocytes (n = 35). **P < 0.01, ***P < 0.001. (C) Representative images for Th17 cells (IL-17+) and Tregs (FoxP3+) infiltration in cervical cancer tissue from the same patient. Immunostained cells (brown, indicated by black arrow) and tumor cells (blue). Magnification,×100.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4359139&req=5

pone.0120855.g001: Th17 cells are highly enriched in tumors of patients with cervical cancer.Th17 cells were gated from CD3+ T cells by flow cytometry. (A) Representative IL-17 expression profiles in CD4+ T cells from the four studied groups. The percentages represent the frequency of Th17 cells among CD4+ T cells. (B) Statistical analysis show that the frequency of Th17 cells was higher in patients with cervical cancer, especially among tumor-infiltrating lymphocytes (n = 35). **P < 0.01, ***P < 0.001. (C) Representative images for Th17 cells (IL-17+) and Tregs (FoxP3+) infiltration in cervical cancer tissue from the same patient. Immunostained cells (brown, indicated by black arrow) and tumor cells (blue). Magnification,×100.
Mentions: To study the distribution of Th17 cells at tumor site, NIL and TIL were isolated from paired nontumor and tumor tissues in 35 patients with cervical cancer and characterized via flow cytometry (Fig. 1A). As expected, the frequency of Th17 cells in tumor tissue, representing 11.49 ± 1.19% of CD4+ T cells, was significantly higher than those in non-tumor tissue (3.68 ± 0.48%, P < 0.001), and peripheral blood of patients with cervical cancer (4.96 ± 0.72%, P < 0.01) and healthy donors (1.67 ± 0.19%, P < 0.001; Fig. 1B). Additionally, the proportion of circulating Th17 cells was also higher in patients with cervical cancer compared with healthy donors (P < 0.001). Immunohistochemical staining also observed substantial Th17 cells in tumor tissue of cervical cancer, even higher than regulatory T cells (Tregs) in the same environment (Fig. 1C). These results collectively suggest that Th17 cells are highly enriched in patients with cervical cancer, especially in tumor tissue.

Bottom Line: However, the source of the increased tumor-infiltrating Th17 cells remains poorly understood.We investigated the prevalence, phenotype and trafficking property of Th17 cells in patients with cervical cancer.In conclusion, Th17 cells are recruited into tumor tissues preferentially through CCR6-CCL20 pathway, which can serve as a novel therapeutic target for cervical cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Hangzhou Obstetrics and Gynecology Hospital, Hangzhou First People's Hospital, Hangzhou, China.

ABSTRACT
Our previous studies suggest that Th17 cells accumulate within tumor tissues and correlate with recurrence of cervical cancer patients. However, the source of the increased tumor-infiltrating Th17 cells remains poorly understood. We investigated the prevalence, phenotype and trafficking property of Th17 cells in patients with cervical cancer. Our results showed that Th17 cells highly aggregated within tumor tissues in an activated phenotype with markedly increased expression of CCR6. Correspondingly, level of CCL20 in the tumor tissues was significantly higher than that in non-tumor and normal control tissues, and strongly positively associated with Th17 cells. Further, in vitro migration assay showed CCL20 had effective chemotaxis to circulating Th17 cells. In conclusion, Th17 cells are recruited into tumor tissues preferentially through CCR6-CCL20 pathway, which can serve as a novel therapeutic target for cervical cancer.

Show MeSH
Related in: MedlinePlus