Details

Autor(en) / Beteiligte

• Whiteside, Theresa L.

Titel

Regulatory T cell subsets in human cancer: are they regulating for or against tumor progression?

Ist Teil von

• Cancer Immunology, Immunotherapy, 2014-01, Vol.63 (1), p.67-72

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• Regulatory T cells (Treg) play a key role in maintaining the balance of immune responses in human health and in disease. Treg come in many flavors and can utilize a variety of mechanisms to modulate immune responses. In cancer, inducible (i) or adaptive Treg expand, accumulate in tissues and the peripheral blood of patients, and represent a functionally prominent component of CD4+ T lymphocytes. Phenotypically and functionally, iTreg are distinct from natural (n) Treg. A subset of iTreg expressing ectonucleotidases, CD39 and CD73, is able to hydrolyze ATP to 5′-AMP and adenosine (ADO) and thus mediate suppression of those immune cells which express ADO receptors. iTeg can also produce prostaglandin E 2 (PGE 2 ). These iTreg, expanding in response to tumor antigens and cytokines such as TGF-β or IL-10, are presumably responsible for the suppression of anti-tumor immune responses and for successful tumor escape. On the other hand, in cancers associated with prominent inflammatory infiltrates, e.g., colorectal carcinoma or certain types of breast cancer, iTreg down-regulate excessive inflammation by producing ADO and/or PGE 2 and protect the host from tissue injury and tumor development. Thus, iTreg utilizing the same adenosine pathway play a key but dual role in cancer, and their plasticity is controlled and driven by the microenvironment. Thus, monitoring for the frequency and functions of iTreg rather than nTreg is important in cancer. In addition, elimination of iTreg by various available strategies prior to immunotherapies may not be beneficial in all cases and needs to be undertaken with caution.