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Cancer immunotherapy: Re-programming cells of the innate and adaptive immune systems.

Manjili MH, Payne KK - Oncoimmunology (2012)

Bottom Line: Cancers utilize multiple mechanisms to overcome immune responses.Emerging evidence suggest that immunotherapy of cancer should focus on inducing and re-programming cells of the innate and adaptive immune systems rather than focusing solely on T cells.Recently, we have shown that such a multifaceted approach can improve immunotherapy of breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology; Virginia Commonwealth University Massey Cancer Center; Richmond, VA USA.

ABSTRACT
Cancers utilize multiple mechanisms to overcome immune responses. Emerging evidence suggest that immunotherapy of cancer should focus on inducing and re-programming cells of the innate and adaptive immune systems rather than focusing solely on T cells. Recently, we have shown that such a multifaceted approach can improve immunotherapy of breast cancer.

No MeSH data available.


Related in: MedlinePlus

Figure 1. Mechanisms by which CD25+ iNKT cells interact with MDSC and rescue T cells from suppression. Tumor-derived soluble factors increase MDSC (A) which in turn suppress anti-tumor T cell responses (B). Activated CD25+ NKT cells interact with CD1d on tumor cells and MDSC and demonstrate enhanced anti-tumor responses (C). This will result in MDSCs increasing expression of CD80/86, CD70, ICAM-1 thus effectively converting to a DC phenotype, which then interacts with CD28 and CD27 on activated T cells, thereby enhancing T cell anti-tumor responses.
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Figure 1: Figure 1. Mechanisms by which CD25+ iNKT cells interact with MDSC and rescue T cells from suppression. Tumor-derived soluble factors increase MDSC (A) which in turn suppress anti-tumor T cell responses (B). Activated CD25+ NKT cells interact with CD1d on tumor cells and MDSC and demonstrate enhanced anti-tumor responses (C). This will result in MDSCs increasing expression of CD80/86, CD70, ICAM-1 thus effectively converting to a DC phenotype, which then interacts with CD28 and CD27 on activated T cells, thereby enhancing T cell anti-tumor responses.

Mentions: Based on these findings we propose a model to explain a cross talk between NKT cells and MDSC as well as with T cells during an effective anti-tumor immune response (Fig. 1). According to this model, double negative (CD4−CD8−) CD25+ invariant NKT (iNKT) cells interact with CD1d on MDSC, resulting in the conversion of MDSC into DC by increasing the expression of CD80/86, CD70 and ICAM-1. Engagement of CD80 and CD70 on newly converted DCs with CD28 and CD27 on T cells support T cell responses to the tumor cells and overcome MDSC suppression. CD25+ iNKT cells can also respond to tumor cells and MDSC in a CD1d-dependent manner. Extensive production of tumor-specific IFNγ by the expanded cells may also overcome tumor relapse that we found to be due to low levels of IFNγ production. This hypothetical model has been supported by our recent publication8 showing that tumor-specific IFNγ production was significantly increased by NKT cells when MDSC were present. In addition, the presence of NKT cells was required in order to overcome MDSC-mediated T cell suppression.


Cancer immunotherapy: Re-programming cells of the innate and adaptive immune systems.

Manjili MH, Payne KK - Oncoimmunology (2012)

Figure 1. Mechanisms by which CD25+ iNKT cells interact with MDSC and rescue T cells from suppression. Tumor-derived soluble factors increase MDSC (A) which in turn suppress anti-tumor T cell responses (B). Activated CD25+ NKT cells interact with CD1d on tumor cells and MDSC and demonstrate enhanced anti-tumor responses (C). This will result in MDSCs increasing expression of CD80/86, CD70, ICAM-1 thus effectively converting to a DC phenotype, which then interacts with CD28 and CD27 on activated T cells, thereby enhancing T cell anti-tumor responses.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3377002&req=5

Figure 1: Figure 1. Mechanisms by which CD25+ iNKT cells interact with MDSC and rescue T cells from suppression. Tumor-derived soluble factors increase MDSC (A) which in turn suppress anti-tumor T cell responses (B). Activated CD25+ NKT cells interact with CD1d on tumor cells and MDSC and demonstrate enhanced anti-tumor responses (C). This will result in MDSCs increasing expression of CD80/86, CD70, ICAM-1 thus effectively converting to a DC phenotype, which then interacts with CD28 and CD27 on activated T cells, thereby enhancing T cell anti-tumor responses.
Mentions: Based on these findings we propose a model to explain a cross talk between NKT cells and MDSC as well as with T cells during an effective anti-tumor immune response (Fig. 1). According to this model, double negative (CD4−CD8−) CD25+ invariant NKT (iNKT) cells interact with CD1d on MDSC, resulting in the conversion of MDSC into DC by increasing the expression of CD80/86, CD70 and ICAM-1. Engagement of CD80 and CD70 on newly converted DCs with CD28 and CD27 on T cells support T cell responses to the tumor cells and overcome MDSC suppression. CD25+ iNKT cells can also respond to tumor cells and MDSC in a CD1d-dependent manner. Extensive production of tumor-specific IFNγ by the expanded cells may also overcome tumor relapse that we found to be due to low levels of IFNγ production. This hypothetical model has been supported by our recent publication8 showing that tumor-specific IFNγ production was significantly increased by NKT cells when MDSC were present. In addition, the presence of NKT cells was required in order to overcome MDSC-mediated T cell suppression.

Bottom Line: Cancers utilize multiple mechanisms to overcome immune responses.Emerging evidence suggest that immunotherapy of cancer should focus on inducing and re-programming cells of the innate and adaptive immune systems rather than focusing solely on T cells.Recently, we have shown that such a multifaceted approach can improve immunotherapy of breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology; Virginia Commonwealth University Massey Cancer Center; Richmond, VA USA.

ABSTRACT
Cancers utilize multiple mechanisms to overcome immune responses. Emerging evidence suggest that immunotherapy of cancer should focus on inducing and re-programming cells of the innate and adaptive immune systems rather than focusing solely on T cells. Recently, we have shown that such a multifaceted approach can improve immunotherapy of breast cancer.

No MeSH data available.


Related in: MedlinePlus