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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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Associations of chemokine levels with intratumoral Th17 cells.(A) Real-time PCR of chemokine CCL17, CCL20 and CCL22 in tumor (T) and non-tumor (nT) regions of patients with cervical cancer and in normal control (NC). The value was normalized to GAPDH, multiplied by 105, and log transformed. *P < 0.05, **P < 0.01. (B, C, D) Correlations of chemokine CCL17 (B), CCL20 (C) and CCL22 (D) with frequency of tumor-infiltrating Th17 cells. Statistical analysis showed a strong correlation of CCL20 with Th17 cells in tumor.
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pone.0120855.g004: Associations of chemokine levels with intratumoral Th17 cells.(A) Real-time PCR of chemokine CCL17, CCL20 and CCL22 in tumor (T) and non-tumor (nT) regions of patients with cervical cancer and in normal control (NC). The value was normalized to GAPDH, multiplied by 105, and log transformed. *P < 0.05, **P < 0.01. (B, C, D) Correlations of chemokine CCL17 (B), CCL20 (C) and CCL22 (D) with frequency of tumor-infiltrating Th17 cells. Statistical analysis showed a strong correlation of CCL20 with Th17 cells in tumor.

Mentions: Because Th17 cells highly expressed CCR6 and CCR4, we hypothesized that Th17 cells could migrate in response to CCL20, CCL22 and CCL17. We determined expression of CCL20, CCL22 and CCL17 by real-time PCR. We found significantly higher mRNA expression of CCL20 in the tumor tissues compared to non-tumor tissues and normal control tissues (P < 0.01, Fig. 4A). Further, a strongly positive correlation was observed between the prevalence of Th17 cells and intra-tumoral expression of CCL20 (R = 0.795, P < 0.001; Fig. 4C). These data suggested that CCL20 is an important signal to mediate the trafficking of Th17 cells to tumors. On the contrary, we did not found increased expression of CCL17 and CCL20, the two specific ligands of CCR4, in tumor tissue (Fig. 4A). Further, regression analysis only found weak correlation of Th17 cells with CCL22 (R = 0.385, P < 0.05; Fig. 4D), but not with CCL17 (P > 0.05, Fig. 4B), in the same tumor microenvironment. The results collectively indicate that CCR4-CCL17/CCL22 axis may not be mainly responsible for Th17-cell migration.


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

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

Associations of chemokine levels with intratumoral Th17 cells.(A) Real-time PCR of chemokine CCL17, CCL20 and CCL22 in tumor (T) and non-tumor (nT) regions of patients with cervical cancer and in normal control (NC). The value was normalized to GAPDH, multiplied by 105, and log transformed. *P < 0.05, **P < 0.01. (B, C, D) Correlations of chemokine CCL17 (B), CCL20 (C) and CCL22 (D) with frequency of tumor-infiltrating Th17 cells. Statistical analysis showed a strong correlation of CCL20 with Th17 cells in tumor.
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Related In: Results  -  Collection

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

pone.0120855.g004: Associations of chemokine levels with intratumoral Th17 cells.(A) Real-time PCR of chemokine CCL17, CCL20 and CCL22 in tumor (T) and non-tumor (nT) regions of patients with cervical cancer and in normal control (NC). The value was normalized to GAPDH, multiplied by 105, and log transformed. *P < 0.05, **P < 0.01. (B, C, D) Correlations of chemokine CCL17 (B), CCL20 (C) and CCL22 (D) with frequency of tumor-infiltrating Th17 cells. Statistical analysis showed a strong correlation of CCL20 with Th17 cells in tumor.
Mentions: Because Th17 cells highly expressed CCR6 and CCR4, we hypothesized that Th17 cells could migrate in response to CCL20, CCL22 and CCL17. We determined expression of CCL20, CCL22 and CCL17 by real-time PCR. We found significantly higher mRNA expression of CCL20 in the tumor tissues compared to non-tumor tissues and normal control tissues (P < 0.01, Fig. 4A). Further, a strongly positive correlation was observed between the prevalence of Th17 cells and intra-tumoral expression of CCL20 (R = 0.795, P < 0.001; Fig. 4C). These data suggested that CCL20 is an important signal to mediate the trafficking of Th17 cells to tumors. On the contrary, we did not found increased expression of CCL17 and CCL20, the two specific ligands of CCR4, in tumor tissue (Fig. 4A). Further, regression analysis only found weak correlation of Th17 cells with CCL22 (R = 0.385, P < 0.05; Fig. 4D), but not with CCL17 (P > 0.05, Fig. 4B), in the same tumor microenvironment. The results collectively indicate that CCR4-CCL17/CCL22 axis may not be mainly responsible for Th17-cell migration.

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