Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic Purposes
The tumor microenvironment (TME) represents a complex network between tumor cells and a variety of components including immune, stromal and vascular endothelial cells as well as the extracellular matrix. A wide panel of signals and interactions here take place, resulting in a bi-directional modulati...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/4/927 |
| _version_ | 1797537301358706688 |
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| author | Claudia Cocco Fabio Morandi Irma Airoldi |
| author_facet | Claudia Cocco Fabio Morandi Irma Airoldi |
| author_sort | Claudia Cocco |
| collection | DOAJ |
| description | The tumor microenvironment (TME) represents a complex network between tumor cells and a variety of components including immune, stromal and vascular endothelial cells as well as the extracellular matrix. A wide panel of signals and interactions here take place, resulting in a bi-directional modulation of cellular functions. Many stimuli, on one hand, induce tumor growth and the spread of metastatic cells and, on the other hand, contribute to the establishment of an immunosuppressive environment. The latter feature is achieved by soothing immune effector cells, mainly cytotoxic T lymphocytes and B and NK cells, and/or through expansion of regulatory cell populations, including regulatory T and B cells, tumor-associated macrophages and myeloid-derived suppressor cells. In this context, immune checkpoints (IC) are key players in the control of T cell activation and anti-cancer activities, leading to the inhibition of tumor cell lysis and of pro-inflammatory cytokine production. Thus, these pathways represent promising targets for the development of effective and innovative therapies both in adults and children. Here, we address the role of different cell populations homing the TME and of well-known and recently characterized IC in the context of pediatric solid tumors. We also discuss preclinical and clinical data available using IC inhibitors alone, in combination with each other or administered with standard therapies. |
| first_indexed | 2024-03-10T12:14:08Z |
| format | Article |
| id | doaj.art-195f365282a644b78067fbd19b76d0cc |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T12:14:08Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-195f365282a644b78067fbd19b76d0cc2023-11-21T15:58:09ZengMDPI AGCells2073-44092021-04-0110492710.3390/cells10040927Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic PurposesClaudia Cocco0Fabio Morandi1Irma Airoldi2Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, IRCCS Istituto Giannina Gaslini, Via G. Gaslini 5, 16147 Genova, ItalyLaboratorio Cellule Staminali Post-Natali e Terapie Cellulari, IRCCS Istituto Giannina Gaslini, Via G. Gaslini 5, 16147 Genova, ItalyLaboratorio Cellule Staminali Post-Natali e Terapie Cellulari, IRCCS Istituto Giannina Gaslini, Via G. Gaslini 5, 16147 Genova, ItalyThe tumor microenvironment (TME) represents a complex network between tumor cells and a variety of components including immune, stromal and vascular endothelial cells as well as the extracellular matrix. A wide panel of signals and interactions here take place, resulting in a bi-directional modulation of cellular functions. Many stimuli, on one hand, induce tumor growth and the spread of metastatic cells and, on the other hand, contribute to the establishment of an immunosuppressive environment. The latter feature is achieved by soothing immune effector cells, mainly cytotoxic T lymphocytes and B and NK cells, and/or through expansion of regulatory cell populations, including regulatory T and B cells, tumor-associated macrophages and myeloid-derived suppressor cells. In this context, immune checkpoints (IC) are key players in the control of T cell activation and anti-cancer activities, leading to the inhibition of tumor cell lysis and of pro-inflammatory cytokine production. Thus, these pathways represent promising targets for the development of effective and innovative therapies both in adults and children. Here, we address the role of different cell populations homing the TME and of well-known and recently characterized IC in the context of pediatric solid tumors. We also discuss preclinical and clinical data available using IC inhibitors alone, in combination with each other or administered with standard therapies.https://www.mdpi.com/2073-4409/10/4/927immune checkpoint inhibitorspediatric solid tumorimmune suppression |
| spellingShingle | Claudia Cocco Fabio Morandi Irma Airoldi Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic Purposes Cells immune checkpoint inhibitors pediatric solid tumor immune suppression |
| title | Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic Purposes |
| title_full | Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic Purposes |
| title_fullStr | Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic Purposes |
| title_full_unstemmed | Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic Purposes |
| title_short | Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic Purposes |
| title_sort | immune checkpoints in pediatric solid tumors targetable pathways for advanced therapeutic purposes |
| topic | immune checkpoint inhibitors pediatric solid tumor immune suppression |
| url | https://www.mdpi.com/2073-4409/10/4/927 |
| work_keys_str_mv | AT claudiacocco immunecheckpointsinpediatricsolidtumorstargetablepathwaysforadvancedtherapeuticpurposes AT fabiomorandi immunecheckpointsinpediatricsolidtumorstargetablepathwaysforadvancedtherapeuticpurposes AT irmaairoldi immunecheckpointsinpediatricsolidtumorstargetablepathwaysforadvancedtherapeuticpurposes |