Significance of Foxp3 Positive Regulatory T Cell and Tumor Infiltrating T Lymphocyte in Triple Negative Breast Cancer

Kang, Hanna; Cheong, Harin; Cho, Min Sun; Koo, Heasoo; Han, Woon Sup; Lee, Jun Young; Moon, Byung In; Sung, Sun Hee

doi:10.4132/koreanjpathol.2011.45.1.53

Cited by 3 publications

(4 citation statements)

References 29 publications

(8 reference statements)

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“…However, in a previous project [ 29 ], we investigated Foxp3 Treg infiltration in TNBC, but found no significant correlation between DFS/OS and Foxp3 Treg. The discrepancy in these results probably stemmed from the intrinsic prognostic difference between the study groups.…”

Section: Discussionmentioning

confidence: 90%

Zonal Difference and Prognostic Significance of Foxp3 Regulatory T Cell Infiltration in Breast Cancer

et al. 2014

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PurposeForkhead box P3 (Foxp3) is known as the most specific marker for regulatory T lymphocytes, which play an important role in immune tolerance to disturb antitumor immunity. The present study aimed to investigate the prognostic significance of Foxp3 regulatory T lymphocyte (Foxp3 Treg) infiltration in breast cancer.MethodsImmunohistochemical studies with Foxp3, CD4, and CD8 were performed on representative full tissue sections from 143 patients with invasive ductal carcinoma, not otherwise specified. Foxp3 Treg infiltration and the ratios between Foxp3 Treg and CD4 or CD8 T cells were separately analyzed for the tumor bed and tumor periphery to evaluate their association with different clinicopathological parameters and patients' outcome.ResultsThe tumor periphery was considerably more densely infiltrated by Foxp3 Treg, CD4, and CD8 T cells than the tumor bed. Unfavorable clinicopathological parameters (a Ki-67 labeling index of ≥14%, a worse histologic grade, a worse nuclear grade, hormone receptor negativity, human epidermal growth factor receptor 2 positivity, and tumor recurrence) were associated with increased Foxp3 Treg infiltration and a high ratio between Foxp3 Treg and CD4/CD8 T cells. In the tumor periphery, as Foxp3 Treg infiltration and the Foxp3 Treg/CD8 ratio increased, patients' 5-year disease-free survival rate decreased.ConclusionThe infiltration densities of Foxp3 Treg, CD4, and CD8 T cells were markedly different between the tumor bed and periphery. Besides the absolute count of Foxp3 Treg, the ratio between Foxp3 Treg and effector T cells was a significant prognostic factor in breast cancer.

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Section: Discussionmentioning

confidence: 90%

Zonal Difference and Prognostic Significance of Foxp3 Regulatory T Cell Infiltration in Breast Cancer

et al. 2014

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“…Finally, the densities of the TIL subpopulations were measured based on IHC staining for CD3, CD8, and CD20, along with a digital microscopic scanner and automated analysis software. Several studies used IHC to evaluate the TIL subpopulations in breast cancer [ 7 , 20 , 25 - 27 ]. On the other hand, most of those studies used semiquantitative methods for the measurements because fully quantitative methods are often difficult and time-consuming due to the large number of TILs.…”

Section: Discussionmentioning

confidence: 99%

Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer

et al. 2017

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PurposeThe tertiary lymphoid structure (TLS) is an important source of tumor-infiltrating lymphocytes (TILs), which have a strong prognostic and predictive value in triple-negative breast cancer (TNBC). A previous study reported that the levels of CXCL13 mRNA expression were associated with TLSs, but measuring the gene expression is challenging in routine practice. Therefore, this study evaluated the MECA79-positive high endothelial venule (HEV) densities and their association with the histopathologically assessed TLSs in biopsy samples. In addition, the relationship of TLSs with the CXCL13 transcript levels and clinical outcomes were examined.Materials and MethodsA total of 108 TNBC patients treated with neoadjuvant chemotherapy (NAC) were studied. The amounts of TILs and TLSs were measured histopathologically using hematoxylin and eosin–stained slides. The HEV densities and TIL subpopulations were measured by immunohistochemistry for MECA79, CD3, CD8, and CD20. CXCL13mRNA expression levels using a NanoString assay (NanoString Technologies).ResultsThe mean number of HEVs in pre-NAC biopsies was 12 (range, 0 to 72). The amounts of TILs and TLSs, HEV density, and CXCL13 expression showed robust correlations with each other. A lower pre-NAC clinical T stage, higher TIL and TLS levels, a higher HEV density, CD20-positive cell density, and CXCL13 expression were significant predictors of a pathologic complete response (pCR). Higher CD8-positive cell density and levels of CXCL13 expression were significantly associated with a better disease-free survival rate.ConclusionMECA79-positive HEV density in pre-NAC biopsies is an objective and quantitative surrogate marker of TLS and might be a valuable tool for predicting pCR of TNBC in routine pathology practice.

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“…55 It has been shown that Tregs are associated with tumor growth in several murine tumor models. In a chemically induced tumor model, progressively growing tumors contained +er percentages of Tregs than rejecting tumors [56]. In a murine model of pancreatic cancer, disruption of homing Tregs inhibited tumor growth.…”

Section: Correlation Between Increased Frequency Of Tregs and Disease Outcome In Cancer Patientsmentioning

confidence: 98%

“…95 In a chemically induced tumor model, tumors were rejected in mice pretreated with anti-CD25 monoclonal antibody. 56 In a neu-transgenic mouse model of breast cancer, Treg depletion with denileukin diftitox immediately after tumor inoculation led to immune-mediated tumor rejection. 96 In a recent study, oral administration of homogenized fibrosarcoma tumor tissue led to systemically increased CD4 + CD25 + Tregs which award a tumor growth advantage in mice.…”

Section: In Vivo Depletion or Blocking Tregs Augmentation Antitumor Immune Responsesmentioning

confidence: 99%

Regulatory T Cells in Cancer Patients and Their Roles in Cancer Development/Progression

Khansari¹

2014

MOJI

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The immune system can protect body against malignant cell formation and cancer development. However, in some cases malignant cells survive and a tumor develops leading to cancer. The immunosuppressive function of some subsets of immune cells is involved in evading the tumor cells from immunosurveillance. In the past decade, elevated levels of regulatory T cells (Tregs) were reported in the peripheral blood and tumor tissue of cancer patients. In most cancer patients, increased levels of Tregs were correlated with poor prognosis. In contrast, increased frequencies of Tregs were associated with favorable prognosis in some cancer patients. So far, the precise roles of Tregs in carcinogenesis and cancer progression have not been addressed. Better understanding of the immunobiology of Tregs is beneficial for elucidation of their roles in cancers and innovation of more effective cancer therapy modalities. In this review, we present extensive information about the immunophenotype and functions of Tregs, mechanisms that are implicated in the recruitment, differentiation, and/or expansion ofthese cells at tumor sites, as well as their frequencies and roles in cancer patients. We also assessed their predictive value in cancer patients.

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Significance of Foxp3 Positive Regulatory T Cell and Tumor Infiltrating T Lymphocyte in Triple Negative Breast Cancer

Cited by 3 publications

References 29 publications

Zonal Difference and Prognostic Significance of Foxp3 Regulatory T Cell Infiltration in Breast Cancer

Zonal Difference and Prognostic Significance of Foxp3 Regulatory T Cell Infiltration in Breast Cancer

Predictive Value of Tertiary Lymphoid Structures Assessed by High Endothelial Venule Counts in the Neoadjuvant Setting of Triple-Negative Breast Cancer

Regulatory T Cells in Cancer Patients and Their Roles in Cancer Development/Progression

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