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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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Phenotypic analysis of Th17 cells in patients with cervical cancer.(A) Representative expression profiles of CD45RO, HLA-DR, Granzyme B and PD-1 in tumor-infiltrating Th17 cells. The percentages represent the frequencies of various markers in Th17 cells. (B) Representative expression profiles of CCR4, CCR6 and CD49d on Th17 cells from peripheral blood (long dotted line), non-tumor (dotted line) and tumor tissues (solid line). The percentages represent the frequencies of various markers on tumor-infiltrating Th17 cells. (C) Statistical analysis of surface expression of CCR4, CCR6, CD49d on Th17 cells from peripheral blood, non-tumor and tumor tissues (n = 25). *P < 0.05, **P < 0.01, ***P < 0.001.
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pone.0120855.g003: Phenotypic analysis of Th17 cells in patients with cervical cancer.(A) Representative expression profiles of CD45RO, HLA-DR, Granzyme B and PD-1 in tumor-infiltrating Th17 cells. The percentages represent the frequencies of various markers in Th17 cells. (B) Representative expression profiles of CCR4, CCR6 and CD49d on Th17 cells from peripheral blood (long dotted line), non-tumor (dotted line) and tumor tissues (solid line). The percentages represent the frequencies of various markers on tumor-infiltrating Th17 cells. (C) Statistical analysis of surface expression of CCR4, CCR6, CD49d on Th17 cells from peripheral blood, non-tumor and tumor tissues (n = 25). *P < 0.05, **P < 0.01, ***P < 0.001.

Mentions: We then analyzed the expression of markers related to activation/effector function (CD45RO and HLA-DR) and immune suppression (granzyme B and PD-1). Tumor-infiltrating Th17 cells expressed high CD45RO, HLA-DR, but low granzyme B and PD-1 (Fig. 3A). Granzyme-B-dependent cytolysis[20] and B7-H1/PD-1 pathway[21] contribute to immune suppression in the tumor microenvironment. These results indicated that tumor-infiltrating Th17 cells exhibited an activated memory phenotype (CD45RO+HLA-DR+) but may not mediate effector function through the granzyme B or B7-H1/PD-1 pathway (Granzyme B-/PD-1-).


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

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

Phenotypic analysis of Th17 cells in patients with cervical cancer.(A) Representative expression profiles of CD45RO, HLA-DR, Granzyme B and PD-1 in tumor-infiltrating Th17 cells. The percentages represent the frequencies of various markers in Th17 cells. (B) Representative expression profiles of CCR4, CCR6 and CD49d on Th17 cells from peripheral blood (long dotted line), non-tumor (dotted line) and tumor tissues (solid line). The percentages represent the frequencies of various markers on tumor-infiltrating Th17 cells. (C) Statistical analysis of surface expression of CCR4, CCR6, CD49d on Th17 cells from peripheral blood, non-tumor and tumor tissues (n = 25). *P < 0.05, **P < 0.01, ***P < 0.001.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0120855.g003: Phenotypic analysis of Th17 cells in patients with cervical cancer.(A) Representative expression profiles of CD45RO, HLA-DR, Granzyme B and PD-1 in tumor-infiltrating Th17 cells. The percentages represent the frequencies of various markers in Th17 cells. (B) Representative expression profiles of CCR4, CCR6 and CD49d on Th17 cells from peripheral blood (long dotted line), non-tumor (dotted line) and tumor tissues (solid line). The percentages represent the frequencies of various markers on tumor-infiltrating Th17 cells. (C) Statistical analysis of surface expression of CCR4, CCR6, CD49d on Th17 cells from peripheral blood, non-tumor and tumor tissues (n = 25). *P < 0.05, **P < 0.01, ***P < 0.001.
Mentions: We then analyzed the expression of markers related to activation/effector function (CD45RO and HLA-DR) and immune suppression (granzyme B and PD-1). Tumor-infiltrating Th17 cells expressed high CD45RO, HLA-DR, but low granzyme B and PD-1 (Fig. 3A). Granzyme-B-dependent cytolysis[20] and B7-H1/PD-1 pathway[21] contribute to immune suppression in the tumor microenvironment. These results indicated that tumor-infiltrating Th17 cells exhibited an activated memory phenotype (CD45RO+HLA-DR+) but may not mediate effector function through the granzyme B or B7-H1/PD-1 pathway (Granzyme B-/PD-1-).

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