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Midgut carcinoid pa...
Midgut carcinoid patients display increased numbers of regulatory T cells in peripheral blood with infiltration into tumor tissue
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- Vikman, Sofia (author)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi
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- Sommaggio, Roberta (author)
- Uppsala universitet,Enheten för klinisk immunologi
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- De La Torre, Manuel (author)
- Uppsala universitet,Institutionen för genetik och patologi
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- Öberg, Kjell (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Endocrine oncology
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- Essand, Magnus (author)
- Uppsala universitet,Enheten för klinisk immunologi
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- Giandomenico, Valeria (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Endocrine Oncology
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- Loskog, Angelica (author)
- Uppsala universitet,Enheten för klinisk immunologi
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- Totterman, Thomas H. (author)
- Uppsala universitet,Enheten för klinisk immunologi,Tötterman
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(creator_code:org_t)
- 2009-07-08
- 2009
- English.
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 48:3, s. 391-400
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Abstract
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- INTRODUCTION: Our aim was to investigate the immune status of midgut carcinoid patients. Cancer patients generally display suppressed Th1-type immunity that disables mounting of an efficient anti-tumor response. However, little is known about patients with neuroendocrine midgut carcinoids. MATERIAL AND METHODS: Circulating regulatory T cells were determined in patient blood by staining for CD4, CD25 and FoxP3 in flow cytometric analysis. T cell proliferation was measured by Alamar Blue in response to polyclonal activation and the regulatory phenotype of patient CD25+ cells was validated by allogeneic stimulation of CFSE labelled responders. Cytokine levels in patient peripheral blood were measured by ELISA and CBA. Tumor infiltrating T cells were analyzed by immunohistochemistry and immunofluorescence. RESULTS: The results demonstrate that midgut carcinoid patients exhibit increased frequencies of circulating Tregs and patient T cells have a decreased proliferative capacity compared to healthy donors. Systemic Th1-promoting cytokines are reduced. Midgut carcinoid tumors display CD4+ and CD8+ T cell infiltration, always in the presence of regulatory CD4+FoxP3+ cells. DISCUSSION: Midgut carcinoid patients display elevated T regulatory cell numbers and T cell dysfunction. Therapeutic strategies to overcome tumor-induced Th1 immunosuppression are required in combination with anti-tumor vaccinations.
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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