Limits...
FOXO3: A master switch for regulating tolerance and immunity in dendritic cells.

Watkins SK, Hurwitz AA - Oncoimmunology (2012)

Bottom Line: Recent findings demonstrate that dendritic cells in prostate tumors induce immune tolerance in tumor antigen-specific CD8(+) T cells.We propose that DC tolerogenicity can be regulated by expression of Foxo3; silencing Foxo3 expression enhances anti-tumor immune responses and renders FOXO3 a potential target for immunotherapy.

View Article: PubMed Central - PubMed

Affiliation: Tumor Immunity and Tolerance Section; Laboratory of Molecular Immunoregulation; Cancer and Inflammation Program; NCI-Frederick; Frederick, MD USA.

ABSTRACT
Recent findings demonstrate that dendritic cells in prostate tumors induce immune tolerance in tumor antigen-specific CD8(+) T cells. We propose that DC tolerogenicity can be regulated by expression of Foxo3; silencing Foxo3 expression enhances anti-tumor immune responses and renders FOXO3 a potential target for immunotherapy.

No MeSH data available.


Related in: MedlinePlus

Increased FOXO3 expression is associated with TADC induced tolerance. (A) TADC produce tolerogenic mediators: IDO, arginase, TGFβ, and express increased PD-L1 and FOXO3. Interaction between TADC and CTLs induced T cell tolerance. (B) Inhibiting Foxo3 or providing a potent pro-inflammatory stimulus converts TADC to immune stimulating and promotes CTL effector functions and anti-tumor immunity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3376981&req=5

Figure 1: Increased FOXO3 expression is associated with TADC induced tolerance. (A) TADC produce tolerogenic mediators: IDO, arginase, TGFβ, and express increased PD-L1 and FOXO3. Interaction between TADC and CTLs induced T cell tolerance. (B) Inhibiting Foxo3 or providing a potent pro-inflammatory stimulus converts TADC to immune stimulating and promotes CTL effector functions and anti-tumor immunity.

Mentions: We initially confirmed that tolerogenic mediators present in the tumor microenvironment (IDO, Arginase, TGFβ) dampened responsiveness of adoptively transferred CD8+ T cells. However, blocking these TADC-derived tolerogenic mediators, individually or in combination, only transiently enhanced T cell effector function. In contrast, depleting TADC restored anti-tumor effector functions of tumor-infiltrating T cells. Subsequent in vitro studies demonstrated that TADC were not only poor stimulators of T cells, but they actively induced T cell tolerance and were capable of inducing suppressive activity, confirming our previous observations using an adoptive transfer model (Fig. 1A).3 Importantly, our results observed in the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model were consistent with studies using TADC isolated from human prostate tumor tissue sections suggesting that our results may have significant clinical relevance.4


FOXO3: A master switch for regulating tolerance and immunity in dendritic cells.

Watkins SK, Hurwitz AA - Oncoimmunology (2012)

Increased FOXO3 expression is associated with TADC induced tolerance. (A) TADC produce tolerogenic mediators: IDO, arginase, TGFβ, and express increased PD-L1 and FOXO3. Interaction between TADC and CTLs induced T cell tolerance. (B) Inhibiting Foxo3 or providing a potent pro-inflammatory stimulus converts TADC to immune stimulating and promotes CTL effector functions and anti-tumor immunity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376981&req=5

Figure 1: Increased FOXO3 expression is associated with TADC induced tolerance. (A) TADC produce tolerogenic mediators: IDO, arginase, TGFβ, and express increased PD-L1 and FOXO3. Interaction between TADC and CTLs induced T cell tolerance. (B) Inhibiting Foxo3 or providing a potent pro-inflammatory stimulus converts TADC to immune stimulating and promotes CTL effector functions and anti-tumor immunity.
Mentions: We initially confirmed that tolerogenic mediators present in the tumor microenvironment (IDO, Arginase, TGFβ) dampened responsiveness of adoptively transferred CD8+ T cells. However, blocking these TADC-derived tolerogenic mediators, individually or in combination, only transiently enhanced T cell effector function. In contrast, depleting TADC restored anti-tumor effector functions of tumor-infiltrating T cells. Subsequent in vitro studies demonstrated that TADC were not only poor stimulators of T cells, but they actively induced T cell tolerance and were capable of inducing suppressive activity, confirming our previous observations using an adoptive transfer model (Fig. 1A).3 Importantly, our results observed in the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model were consistent with studies using TADC isolated from human prostate tumor tissue sections suggesting that our results may have significant clinical relevance.4

Bottom Line: Recent findings demonstrate that dendritic cells in prostate tumors induce immune tolerance in tumor antigen-specific CD8(+) T cells.We propose that DC tolerogenicity can be regulated by expression of Foxo3; silencing Foxo3 expression enhances anti-tumor immune responses and renders FOXO3 a potential target for immunotherapy.

View Article: PubMed Central - PubMed

Affiliation: Tumor Immunity and Tolerance Section; Laboratory of Molecular Immunoregulation; Cancer and Inflammation Program; NCI-Frederick; Frederick, MD USA.

ABSTRACT
Recent findings demonstrate that dendritic cells in prostate tumors induce immune tolerance in tumor antigen-specific CD8(+) T cells. We propose that DC tolerogenicity can be regulated by expression of Foxo3; silencing Foxo3 expression enhances anti-tumor immune responses and renders FOXO3 a potential target for immunotherapy.

No MeSH data available.


Related in: MedlinePlus