FOXP3 Expression and Overall Survival in Breast Cancer

Merlo, Andrea; Casalini, Patrizia; Carcangiu, Maria Luisa; Malventano, Chiara; Triulzi, Tiziana; Ménard, Sylvie; Tagliabue, Elda; Balsari, Andrea

doi:10.1200/jco.2008.17.9036

Cited by 269 publications

(292 citation statements)

References 24 publications

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“…However, due to late presentation and delayed diagnosis, the timing of Treg expansion in pancreatic cancer is difficult to assess. Moreover, in contrast to findings in ovarian carcinoma and breast cancer (21,22), Treg frequency appears not to be correlated with poor survival in pancreatic carcinoma patients. However, since our study only investigated patients with locally advanced or metastatic cancer, the significance of Tregs as potential prognostic and predictive indicators must be evaluated prospectively, in a large cohort of patients with operable tumors.…”

Section: Tgf-β1 -----------------------------------------------------mentioning

confidence: 47%

Potential plasticity of T regulatory cells in pancreatic carcinoma in relation to disease progression and outcome

Vizio

Novarino

Giacobino

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. CD4+ CD25 + FoxP3 + regulatory T cells (Tregs) are understood to maintain peripheral tolerance to self-antigens and inhibit antitumor immune responses. However, compelling evidence suggests that, Tregs provide no anti-inflammatory protection in the tumor microenvironment, but rather contribute to a T helper 17 (Th17)-driven pro-carcinogenic process. Using three-color flow cytometry, we evaluated the percentage of circulating CD4 + CD25 + FoxP3 + Tregs in the peripheral blood of pancreatic carcinoma patients prior to and after chemotherapy [gemcitabine (GEM) alone, or GEM+oxaliplatin (GEMOX) or bevacizumab+capecitabine+ radiotherapy (BEV+CAPE+RT)]. Correlations were sought between Treg counts and plasma levels of cytokines relevant to controlling the Treg/Th17 balance, i.e., interleukin (IL)-23, IL-17A, IL-6 and transforming growth factor β 1 (TGF-β1), as measured by ELISA and the clinical features of pancreatic cancer. Treg, IL-6 and TGF-β1 levels were higher in locally advanced and metastatic pancreatic carcinoma patients compared to controls. No parameter was correlated with disease stage except IL-6. IL-17A and TGF-β1 were significantly associated with increased risk of poor prognosis. IL-17A was positively correlated with IL-23. Treg and IL-6 levels decreased following GEM monochemotherapy, IL-17A levels decreased after GEMOX, and IL-6 levels were reduced subsequent to BEV+CAPE+RT treatment. IL-23, IL-17A and TGF-β1 levels were significantly lower in patients responding to chemotherapy (partial remission/stable disease) than in nonresponders to chemotherapy (progressive disease). These results suggest an impact of the Treg/Th17-balance in pancreatic carcinoma, highlighting the significance of TGF-β1 and IL-17A as potential prognostic and predictive indicators. Immunological changes induced by mono and/or combined chemotherapy indicate specific windows of opportunity for introducing integrative interventions on a new target in pancreatic cancer, i.e. IL-17A, possibly improving survival in this highly lethal disease.

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Section: Tgf-β1 -----------------------------------------------------mentioning

confidence: 47%

Potential plasticity of T regulatory cells in pancreatic carcinoma in relation to disease progression and outcome

Vizio

Novarino

Giacobino

et al. 2012

Experimental and Therapeutic Medicine

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“…B7H1 expression was associated with the presence of a mixture of immune cells infiltrating tumor samples including FOXP3C lymphocytes, which we recently demonstrated associated with DTC features of aggressiveness (Cunha et al 2012b). These lymphocytes may provoke a molecular mimicry that enables immune evasion (Hinz et al 2007) and modulates patterns of molecule expression in tumor cells, thus favoring an aggressive phenotype (Merlo et al 2009). Many reports have shown that B7H1 frequently avoids cancer cell immune destruction despite the presence of different immune cells infiltrating the tumor microenvironment , Hua et al 2012, Taube et al 2012.…”

Section: Discussionmentioning

confidence: 99%

Differentiated thyroid carcinomas may elude the immune system by B7H1 upregulation

Cunha¹,

Marcello²,

Morari³

et al. 2012

Endocrine-Related Cancer

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B7H1 is consistently associated with inhibition of the immune system in many solid tumors. However, there is no report about its impact on differentiated thyroid carcinoma (DTC) presentation, aggressiveness, or evolution. Aiming to investigate the role of B7H1 in DTC and correlate this protein with other tumor-infiltrating immune cells, we studied 407 thyroid nodule tissue samples including 293 from DTC patients, all managed according to a same standard protocol. In addition, we obtained 5 normal and 114 benign thyroid lesions. Eighteen out of the 253 papillary thyroid carcinomas were paired with respective metastatic lymph node tissues. B7H1 (CD274) protein expression was assessed by immunohistochemistry and the gene expression was quantified by real-time PCR. Malignant tissues displayed a more intense B7H1 staining and higher mRNA levels than benign tissues (both P!0.0001). We observed a positive linear correlation between higher age at diagnosis and B7H1 mRNA levels (PZ0.02896). Elevated levels of B7H1 protein were associated with the presence of CD4C, CD8C, CD20C, and FoxP3C lymphocytes (all P!0.05); tumor-associated macrophages (P!0.0001); and the presence of myeloid-derived suppressor cells (PZ0.03256). Stage II-IV patients presented higher B7H1 mRNA levels than stage I cases (PZ0.03522). On the contrary, a decreased expression of B7H1 protein was observed in lymph node metastasis (PZ0.0152). In conclusion, our data demonstrate that B7H1 expression is associated with features of aggressiveness, suggesting that this is an immune evasion mechanism of DTC cells.

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“…However, a predominant cytoplasmic FOXP3 labeling was reported for human pancreatic cancer cells (Hinz et al, 2007). In a recent work dealing with two large series of breast cancer specimens, immunohistological FOXP3 staining was localized predominantly in the tumor cell cytoplasm, whereas a few specimens showed only nuclear staining (Merlo et al, 2009). Finally, in a series of 103 human breast cancers selected for HER-2 oncogene overexpression, FOXP3 was observed in cancer cells of 59 specimens, but only with a cytoplasmic localization, without any nuclear extension (Figure 3) (Ladoire et al,…”

Section: Antioncogenic Effect Of Foxp3mentioning

confidence: 97%

Human FOXP3 and cancer

et al. 2010

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FOXP3 is a transcription factor necessary and sufficient for induction of the immunosuppressive functions in regulatory T lymphocytes. Its expression was first considered as specific of this cell type, but FOXP3 can also be transiently expressed in T-cell antigen receptoractivated human nonregulatory T cells. Recent data indicate that FOXP3 is also expressed by some nonlymphoid cells, in which it can repress various oncogenes that are restored following FOXP3 deletion or mutation. This review summarizes major advances in (1) the understanding of Foxp3 functions in human regulatory T cells, (2) the prognostic significance of Foxp3-expressing T cells in human malignancies and (3) the significance of Foxp3 expression in human tumor cells.

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FOXP3 Expression and Overall Survival in Breast Cancer

Abstract: The data identify FOXP3 expression as a new independent prognostic factor in breast carcinoma, which might help to improve the selection of patients for appropriate therapy.

Cited by 269 publications

References 24 publications

Potential plasticity of T regulatory cells in pancreatic carcinoma in relation to disease progression and outcome

Potential plasticity of T regulatory cells in pancreatic carcinoma in relation to disease progression and outcome

Differentiated thyroid carcinomas may elude the immune system by B7H1 upregulation

Human FOXP3 and cancer

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