Simultaneous Foxp3 and IDO expression is associated with sentinel lymph node metastases in breast cancerReport as inadecuate

Simultaneous Foxp3 and IDO expression is associated with sentinel lymph node metastases in breast cancer - Download this document for free, or read online. Document in PDF available to download.

BMC Cancer

, 9:231

First Online: 15 July 2009Received: 23 February 2009Accepted: 15 July 2009DOI: 10.1186-1471-2407-9-231

Cite this article as: Mansfield, A.S., Heikkila, P.S., Vaara, A.T. et al. BMC Cancer 2009 9: 231. doi:10.1186-1471-2407-9-231


BackgroundThere is evidence that the immune systems of patients with breast cancer are dysfunctional. Regulatory T cells Tregs, and IDO, an immunosuppressive enzyme, are associated with more advanced disease in some cancers and may promote immunologic tolerance to tumors. Our aim was to assess whether expression of Foxp3, a marker of Tregs, and IDO were linked with nodal metastasis in breast cancer patients. Inhibitors of IDO are available and could potentially demonstrate utility in breast cancer if IDO drives progression of disease.

MethodsSentinel lymph nodes SLN of 47 breast cancer patients with varying degrees of nodal disease and 10 controls were evaluated for expression of Foxp3 and IDO using immunohistochemistry. Positively stained cells were quantified and their distribution within the SLN noted.

ResultsThe proportion of Foxp3 cells was higher in SLN of cancer patients than controls 19% v. 10%, p < 0.001. Specifically, there were more Foxp3 cells in SLN with metastasis than tumor-free SLN 20% v. 14%, p = 0.02. The proportion IDO cell in SLN of cancer patients was not statistically different than controls 4.0% v. 1.6%, p = 0.08. In order to demonstrate the combined immunosuppressive effect of Foxp3 and IDO, we categorized each SLN as positive or negative for Foxp3 and IDO. The Foxp3-IDO group almost exclusively consisted of cancer patients with node positive disease.

ConclusionIn conclusion, our study shows that Foxp3 cells are associated with more advanced disease in breast cancer, a finding that is proving to be true in many other cancers. As IDO has been found to promote differentiation of Tregs, IDO may become a suitable target to abrogate the development of T-cell tolerance and to promote an effective immune response to breast cancer. Our results about the combined expression of IDO and Foxp3 in metastastic SLN support this assumption.

AbbreviationsSLNsentinel lymph nodes

Tregsregulatory T-cells

IDOindolamine 2,3-dioxygenase

DCISductal carcinoma in situ

ERestrogen receptor

PRprogesterone receptor

MIB-1proliferation index.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-9-231 contains supplementary material, which is available to authorized users.

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Author: Aaron S Mansfield - Paivi S Heikkila - Ari T Vaara - Karl AJ von Smitten - Jukka M Vakkila - Marjut HK Leidenius


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