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Regulatory T cells in colorectal cancer: from biology to prognostic relevance.

Mougiakakos D - Cancers (Basel) (2011)

Bottom Line: Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders.Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control.This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology and Pathology, Immune and Gene Therapy Unit, Cancer Centre Karolinska, CCK R8:01, 17176 Stockholm, Sweden. dimitrios.mougiakakos@ki.se.

ABSTRACT
Regulatory T cells (Tregs) were initially described as "suppressive" lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches.

No MeSH data available.


Related in: MedlinePlus

Accumulation of regulatory T cells in cancer. A number of mechanisms lead to the observed accumulation of regulatory T cells (Tregs) in cancer. Malignant cells and/or bystanding fibroblasts, dendritic cells (DCs) as well as tumor associated macrophages (TAMs) in the tumor stroma produce and secrete several chemokines, which are chemoattractive for Tregs and result in their recruitment from the circulation away to the tumor site. Pre-existing Tregs can clonally expand upon antigen-specific activation in presence of mainly TGF-β and IL-10 that are regularly found at high levels within the tumor microenvironment. These two cytokines together with a suboptimal antigen presentation that is provided by tolerogenic DCs, TAMs and/or myeloid derived suppressor cells (MDSCs) additionally promote the conversion of conventional T cells (Tconv) into suppressive, adaptive Tregs including naturally occuring (n) Treg-like, T helper (h) 3 and T regulatory (r) 1 cells.
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f1-cancers-03-01708: Accumulation of regulatory T cells in cancer. A number of mechanisms lead to the observed accumulation of regulatory T cells (Tregs) in cancer. Malignant cells and/or bystanding fibroblasts, dendritic cells (DCs) as well as tumor associated macrophages (TAMs) in the tumor stroma produce and secrete several chemokines, which are chemoattractive for Tregs and result in their recruitment from the circulation away to the tumor site. Pre-existing Tregs can clonally expand upon antigen-specific activation in presence of mainly TGF-β and IL-10 that are regularly found at high levels within the tumor microenvironment. These two cytokines together with a suboptimal antigen presentation that is provided by tolerogenic DCs, TAMs and/or myeloid derived suppressor cells (MDSCs) additionally promote the conversion of conventional T cells (Tconv) into suppressive, adaptive Tregs including naturally occuring (n) Treg-like, T helper (h) 3 and T regulatory (r) 1 cells.

Mentions: Accumulation of Tregs has been described in cancer patients for the tumor microenvironment- as well as systemically [32]. As yet in vitro as well as in vivo observations have revealed a complex underlying system that comprises recruitment, expansion and de novo generation of Tregs (Figure 1).


Regulatory T cells in colorectal cancer: from biology to prognostic relevance.

Mougiakakos D - Cancers (Basel) (2011)

Accumulation of regulatory T cells in cancer. A number of mechanisms lead to the observed accumulation of regulatory T cells (Tregs) in cancer. Malignant cells and/or bystanding fibroblasts, dendritic cells (DCs) as well as tumor associated macrophages (TAMs) in the tumor stroma produce and secrete several chemokines, which are chemoattractive for Tregs and result in their recruitment from the circulation away to the tumor site. Pre-existing Tregs can clonally expand upon antigen-specific activation in presence of mainly TGF-β and IL-10 that are regularly found at high levels within the tumor microenvironment. These two cytokines together with a suboptimal antigen presentation that is provided by tolerogenic DCs, TAMs and/or myeloid derived suppressor cells (MDSCs) additionally promote the conversion of conventional T cells (Tconv) into suppressive, adaptive Tregs including naturally occuring (n) Treg-like, T helper (h) 3 and T regulatory (r) 1 cells.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3757386&req=5

f1-cancers-03-01708: Accumulation of regulatory T cells in cancer. A number of mechanisms lead to the observed accumulation of regulatory T cells (Tregs) in cancer. Malignant cells and/or bystanding fibroblasts, dendritic cells (DCs) as well as tumor associated macrophages (TAMs) in the tumor stroma produce and secrete several chemokines, which are chemoattractive for Tregs and result in their recruitment from the circulation away to the tumor site. Pre-existing Tregs can clonally expand upon antigen-specific activation in presence of mainly TGF-β and IL-10 that are regularly found at high levels within the tumor microenvironment. These two cytokines together with a suboptimal antigen presentation that is provided by tolerogenic DCs, TAMs and/or myeloid derived suppressor cells (MDSCs) additionally promote the conversion of conventional T cells (Tconv) into suppressive, adaptive Tregs including naturally occuring (n) Treg-like, T helper (h) 3 and T regulatory (r) 1 cells.
Mentions: Accumulation of Tregs has been described in cancer patients for the tumor microenvironment- as well as systemically [32]. As yet in vitro as well as in vivo observations have revealed a complex underlying system that comprises recruitment, expansion and de novo generation of Tregs (Figure 1).

Bottom Line: Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders.Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control.This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology and Pathology, Immune and Gene Therapy Unit, Cancer Centre Karolinska, CCK R8:01, 17176 Stockholm, Sweden. dimitrios.mougiakakos@ki.se.

ABSTRACT
Regulatory T cells (Tregs) were initially described as "suppressive" lymphocytes in the 1980s. However, it took almost 20 years until the concept of Treg-mediated immune control in its present form was finally established. Tregs are obligatory for self-tolerance and defects within their population lead to severe autoimmune disorders. On the other hand Tregs may promote tolerance for tumor antigens and even hamper efforts to overcome it. Intratumoral and systemic accumulation of Tregs has been observed in various types of cancer and is often linked to worse disease course and outcome. Increase of circulating Tregs, as well as their presence in mesenteric lymph nodes and tumor tissue of patients with colorectal cancer de facto suggests a strong involvement of Tregs in the antitumor control. This review will focus on the Treg biology in view of colorectal cancer, means of Treg accumulation and the controversies regarding their prognostic significance. In addition, a concise overview will be given on how Tregs and their function can be targeted in cancer patients in order to bolster an inherent immune response and/or increase the efficacy of immunotherapeutic approaches.

No MeSH data available.


Related in: MedlinePlus