Clinical implications of co-inhibitory molecule expression in the tumor microenvironment for DC vaccination: a game of stop and go
The aim of therapeutic dendritic cell (DC) vaccines in cancer immunotherapy is to activate cytotoxic T cells to recognize and attack the tumor. T cell activation requires the interaction of the T cell receptor with a cognate major histocompatibility complex (MHC)-peptide complex. Although initiated...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2013-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00417/full |
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| author | Angela eVasaturo Stefania eDi Blasio Deborah G.A. Peeters Coco C.H. De Koning Jolanda eDe Vries Jolanda eDe Vries Carl eFigdor Stanleyson Valentino Hato |
| author_facet | Angela eVasaturo Stefania eDi Blasio Deborah G.A. Peeters Coco C.H. De Koning Jolanda eDe Vries Jolanda eDe Vries Carl eFigdor Stanleyson Valentino Hato |
| author_sort | Angela eVasaturo |
| collection | DOAJ |
| description | The aim of therapeutic dendritic cell (DC) vaccines in cancer immunotherapy is to activate cytotoxic T cells to recognize and attack the tumor. T cell activation requires the interaction of the T cell receptor with a cognate major histocompatibility complex (MHC)-peptide complex. Although initiated by antigen engagement, it is the complex balance between co-stimulatory and co-inhibitory signals on DCs that results in T cell activation or tolerance. Even when already activated, tumor-specific T cells can be neutralized by the expression of co-inhibitory molecules on tumor cells. These and other immunosuppressive cues in the tumor microenvironment are major factors currently hampering the application of DC vaccination. In this review, we discuss recent data regarding the essential and complex role of co-inhibitory molecules in regulating the immune response within the tumor microenvironment. In particular, possible therapeutic intervention strategies aimed at reversing or neutralizing suppressive networks within the tumor microenvironment will be emphasized. Importantly, blocking co-inhibitory molecule signaling, often referred to as immune checkpoint blockade, does not necessarily lead to an effective activation of tumor-specific T cells. Therefore, combination of checkpoint blockade with other immune potentiating therapeutic strategies, such as DC vaccination, might serve as a synergistic combination, capable of reversing effector T cells immunosuppression while at the same time increasing the efficacy of T cell-mediated immunotherapies. This will ultimately result in long-term anti-tumor immunity. |
| first_indexed | 2024-12-22T03:56:16Z |
| format | Article |
| id | doaj.art-310e5cd9bbbe4513a39ab60773bb0801 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T03:56:16Z |
| publishDate | 2013-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-310e5cd9bbbe4513a39ab60773bb08012022-12-21T18:39:51ZengFrontiers Media S.A.Frontiers in Immunology1664-32242013-12-01410.3389/fimmu.2013.0041770393Clinical implications of co-inhibitory molecule expression in the tumor microenvironment for DC vaccination: a game of stop and goAngela eVasaturo0Stefania eDi Blasio1Deborah G.A. Peeters2Coco C.H. De Koning3Jolanda eDe Vries4Jolanda eDe Vries5Carl eFigdor6Stanleyson Valentino Hato7Nijmegen Centre for Molecular LifeSciences, Radboud University Medical CenterNijmegen Centre for Molecular LifeSciences, Radboud University Medical CenterNijmegen Centre for Molecular LifeSciences, Radboud University Medical CenterNijmegen Centre for Molecular LifeSciences, Radboud University Medical CenterNijmegen Centre for Molecular LifeSciences, Radboud University Medical CenterNijmegen Centre for Molecular LifeSciences, Radboud University Medical CentreNijmegen Centre for Molecular LifeSciences, Radboud University Medical CenterNijmegen Centre for Molecular LifeSciences, Radboud University Medical CenterThe aim of therapeutic dendritic cell (DC) vaccines in cancer immunotherapy is to activate cytotoxic T cells to recognize and attack the tumor. T cell activation requires the interaction of the T cell receptor with a cognate major histocompatibility complex (MHC)-peptide complex. Although initiated by antigen engagement, it is the complex balance between co-stimulatory and co-inhibitory signals on DCs that results in T cell activation or tolerance. Even when already activated, tumor-specific T cells can be neutralized by the expression of co-inhibitory molecules on tumor cells. These and other immunosuppressive cues in the tumor microenvironment are major factors currently hampering the application of DC vaccination. In this review, we discuss recent data regarding the essential and complex role of co-inhibitory molecules in regulating the immune response within the tumor microenvironment. In particular, possible therapeutic intervention strategies aimed at reversing or neutralizing suppressive networks within the tumor microenvironment will be emphasized. Importantly, blocking co-inhibitory molecule signaling, often referred to as immune checkpoint blockade, does not necessarily lead to an effective activation of tumor-specific T cells. Therefore, combination of checkpoint blockade with other immune potentiating therapeutic strategies, such as DC vaccination, might serve as a synergistic combination, capable of reversing effector T cells immunosuppression while at the same time increasing the efficacy of T cell-mediated immunotherapies. This will ultimately result in long-term anti-tumor immunity.http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00417/fullTumor Microenvironmentcancer treatmentcheckpoint blockadeDC vaccinationtumor-specific T cells |
| spellingShingle | Angela eVasaturo Stefania eDi Blasio Deborah G.A. Peeters Coco C.H. De Koning Jolanda eDe Vries Jolanda eDe Vries Carl eFigdor Stanleyson Valentino Hato Clinical implications of co-inhibitory molecule expression in the tumor microenvironment for DC vaccination: a game of stop and go Frontiers in Immunology Tumor Microenvironment cancer treatment checkpoint blockade DC vaccination tumor-specific T cells |
| title | Clinical implications of co-inhibitory molecule expression in the tumor microenvironment for DC vaccination: a game of stop and go |
| title_full | Clinical implications of co-inhibitory molecule expression in the tumor microenvironment for DC vaccination: a game of stop and go |
| title_fullStr | Clinical implications of co-inhibitory molecule expression in the tumor microenvironment for DC vaccination: a game of stop and go |
| title_full_unstemmed | Clinical implications of co-inhibitory molecule expression in the tumor microenvironment for DC vaccination: a game of stop and go |
| title_short | Clinical implications of co-inhibitory molecule expression in the tumor microenvironment for DC vaccination: a game of stop and go |
| title_sort | clinical implications of co inhibitory molecule expression in the tumor microenvironment for dc vaccination a game of stop and go |
| topic | Tumor Microenvironment cancer treatment checkpoint blockade DC vaccination tumor-specific T cells |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00417/full |
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