Distribution of Th17 cells and Foxp3-expressing T cells in tumor-infiltrating lymphocytes in patients with uterine cervical cancer

Hou, Fei; Li, Zhen; Ma, Daoxin; Zhang, Wenjing; Zhang, Youzhong; Zhang, Tingguo; Kong, Beihua; Cui, Baoxia

doi:10.1016/j.cca.2012.07.012

Cited by 37 publications

(51 citation statements)

References 37 publications

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“…Researchers believe that FOXP3 expression is an independent risk factor for breast cancer metastasis [30,31]. In a study of FOXP3 gene and cervical cancer, Hou et al [32] showed that an imbalance of the immune system was present in patients with cervical cancer, which led to T cells differentiating towards FOXP3 + T cells. Therefore, the population of FOXP3 + T cells was significantly higher in patients with cervical cancer than in healthy subjects.…”

Section: Discussionmentioning

confidence: 98%

FOXP3 autoantibody as a potential early prognostic serum biomarker in patients with cervical cancer

Huangfu

Jia

et al. 2015

Int J Clin Oncol

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Section: Discussionmentioning

confidence: 98%

FOXP3 autoantibody as a potential early prognostic serum biomarker in patients with cervical cancer

Huangfu

Jia

et al. 2015

Int J Clin Oncol

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“…Recent studies demonstrated that Th17 cells infiltrate cervical precursor lesions and that their numbers further increase in cervical cancers (18). So far it was unclear, how Th17 cells are recruited.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, Th17 cells, a novel T-cell subset with potent proinflammatory and protumorigenic properties (14)(15)(16)(17), were detected in biopsies of patients with high-grade intraepithelial lesions as well as in their peripheral blood (18,19). Notably, the number of infiltrating Th17 cells further increases with progression to invasive cervical cancer (18).…”

Section: Introductionmentioning

confidence: 99%

Stromal Fibroblasts Induce CCL20 through IL6/C/EBPβ to Support the Recruitment of Th17 Cells during Cervical Cancer Progression

et al. 2015

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Cervical cancer is a consequence of persistent infection with human papillomaviruses (HPV). Progression to malignancy is linked to an inflammatory microenvironment comprising T-helper-17 (Th17) cells, a T-cell subset with protumorigenic properties. Neoplastic cells express only low endogenous levels of the Th17 chemoattractant CCL20, and therefore, it is unclear how Th17 cells are recruited to the cervical cancer tissue. In this study, we demonstrate that CCL20 was predominantly expressed in the stroma of cervical squamous cell carcinomas in situ. This correlated with stromal infiltration of CD4 þ /IL17 þ cells and with advancing International Federation of Gynecology and Obstetrics (FIGO) stage. Furthermore, we show that cervical cancer cells instructed primary cervical fibroblasts to produce high levels of CCL20 and to attract CD4/IL17/CCR6-positive cells, generated in vitro, in a CCL20/CCR6-dependent manner. Further mechanistic investigations identified cervical cancer cell-derived IL6 as an important mediator of paracrine CCL20 induction at the promoter, mRNA, and protein level in fibroblasts. CCL20 was upregulated through the recently described CCAAT/enhancerbinding protein b (C/EBPb) pathway as shown with a dominantnegative version of C/EBPb and through siRNA-mediated knockdown. In summary, our study defines a novel molecular mechanism by which cervical neoplastic cells shape their local microenvironment by instructing fibroblasts to support Th17 cell infiltration in a paracrine IL6/C/EBPb-dependent manner. Th17 cells may in turn maintain chronic inflammation within highgrade cervical lesions to further promote cancer progression.Cancer Res; 75(24); 5248-59. Ó2015 AACR.

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“…Interestingly, a recent study showed that the upregulation of Foxp3 expression by T regs and increase of Th17 cells simultaneously occurred in NOD mice fed acidic water, which was associated with an alteration in the gut microbiome and a decreased risk of diabetes [47]. However, Th17 cells and T regs are also frequently most abundant in other anatomical compartments, such as inflamed synovial fluids [48], and in cancerous tissues, such as aggressively growing breast cancer [49], uterine cervical cancer [50], colorectal cancer [51], gastric cancer [52], and malignant pleural effusion [53] in humans, as well as a number of mouse tumor models, including gliomas [54]. Therefore, the physiological relevance of colocalization of these two subsets of CD4 cells likely does more than maintain defense against invading pathogen and tolerance to self-tissues.…”

Section: Th17 Cells and T Regs Frequently Colocalize In The Same Anatmentioning

confidence: 95%

Th17 cells and Tregs: unlikely allies

Chen

Oppenheim

2014

Journal of Leukocyte Biology

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Identification of CD4Foxp3 T and Th17 modified the historical Th1-Th2 paradigm. Currently, the Th17-T dichotomy provides a dominant conceptual framework for the comprehension of immunity/inflammation and tolerance/immunosuppression in an increasing number of diseases. Targeting proinflammatory Th17 cells or immunosuppressive T has been widely considered as a promising therapeutic strategy in the treatment of major human diseases, including autoimmunity and cancer. The efficacy and safety of such therapy rely on a thorough understanding of immunobiology and interaction of these two subsets of Th cells. In this article, we review recent progress concerning complicated interplay of Th17 cells and T There is compelling evidence that T potently inhibit Th1 and Th2 responses; however, the inhibitory effect of T on Th17 responses is a controversial subject. There is increasing evidence showing that T actually promote the differentiation of Th17 cells in vitro and in vivo and consequently, enhanced the functional consequences of Th17 cells, including the protective effect in host defense, as well as detrimental effect in inflammation and in the support of tumor growth. On the other hand, Th17 cells were also the most potent Th subset in the stimulation and support of expansion and phenotypic stability of T in vivo. These results indicate that these two subsets of Th cells reciprocally stimulate each other. This bidirectional crosstalk is largely dependent on the TNF-TNFR2 pathway. These mutual stimulatory effects should be considered in devising future Th17 cell- and T-targeting therapy.

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Distribution of Th17 cells and Foxp3-expressing T cells in tumor-infiltrating lymphocytes in patients with uterine cervical cancer

Cited by 37 publications

References 37 publications

FOXP3 autoantibody as a potential early prognostic serum biomarker in patients with cervical cancer

FOXP3 autoantibody as a potential early prognostic serum biomarker in patients with cervical cancer

Stromal Fibroblasts Induce CCL20 through IL6/C/EBPβ to Support the Recruitment of Th17 Cells during Cervical Cancer Progression

Th17 cells and Tregs: unlikely allies

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