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- Title
Midgut carcinoid patients display increased numbers of regulatory T cells in peripheral blood with infiltration into tumor tissue.
- Authors
Vikman, Sofia; Sommaggio, Roberta; De La Torre, Manuel; Öberg, Kjell; Essand, Magnus; Giandomenico, Valeria; Loskog, Angelica; Tötterman, Thomas H.
- Abstract
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.
- Subjects
CARCINOID; NEUROENDOCRINE tumors; T cells; CANCER patients; CHROMAFFIN cell tumors
- Publication
Acta Oncologica, 2009, Vol 48, Issue 3, p391
- ISSN
0284-186X
- Publication type
Article
- DOI
10.1080/02841860802438495