Primary malignant brain tumors (PMBT) are among the most extensively diagnosed tumors in
children throughout the world. They comprise many histological subcategories and are the
principal cause of cancer related death in children from birth to adolescence. The exclusive biology of the brain and its microenvironment are significant common features of this assorted group of diseases. Their complexity represents an additional degree of difficulty in understanding the fundamental biological processes and development of new effective therapies.
Therefore, in the effort to identify new therapeutic targets, the PMBT tumor microenvironment (TME) remains to be the top research interest. The TME in PMBT changes with the disease progression, and its composition can adapt under the pressure of treatment such as surgical resection, radiotherapy or chemotherapy. Moreover, the TME is central to tumorigenesis, tumor expansion and metastasis development. The TME is very complex containing not only tumor cells but also several types of supporting cell types (activated fibroblasts, blood vessels, penetrating immune cells and extracellular matrix), additional cells, hormones and inflammatory responses. Therefore, deep understanding of the TME represents an essential aspect in the prevention, diagnosis and treatment of those tumors.
Over the decades the community of scientists studied the PMBT TME by co-culturing tumor cells with external immune cells using the common 2D “invitro” models and/or humanized mouse models, such as, genetically engineered mouse models (GEMM) and Patient-derived xenografts (PDX). Unfortunately, they found many limitations in preclinical drug testing and addressing mechanism of tumorigenesis.
To address these limitations, 3D “invitro” models (organoids) emerged as newly developed
technique to connect the gap between 2D systems and animal models. In fact, organoid
technologies are able to resemble the cancer tissue architecture in more authentic way,
recapturing both the tumor cells and the stromal matrix of the tumor microenvironment by
using human cells. Moreover, organoid models can replace the use of mice while allowing
scientists to have more direct access to the cellular processes in brain tissue. In addition,
organoid models are particularly useful for the study of cell-cell interactions, tumor invasion,
cellular migration and tumor-immune interactions.
Despite all the advantages organoid technologies represents, the challenge still remains to
authentically mimic the TME of brain tumors. Since naïve organoid are lacking immune cell and
vasculature to study TME, 3D “invitro” tumor models can be designed to be equipped with
these features by forming a chimera called “assembloid”. The characteristics of 3D “invitro”
tumor models can be also adapted to the specific applications purpose: organoid/immune cell
co-culture, air liquid interface, 3D microfluidic and 3D-Bioprintig models.
This research topic aims to provide an overview of newly developed 3D “invitro” preclinical
models designed to study brain tumor-immune system interactions as well as the latest
advancements of brain cancer immunotherapy.
This may include but are not limited to the following sub-topics:
1. Methodology to derive brain TME using both patient derived organoid and induced
pluripotent stem cell (iPSC) brain organoid.
2. Methodology using 3D “invitro” models to study the interaction between PMBT TME
and brain microenvironment.
3. Methodology using 3D “invitro” models to study the immune cells invasion of PMBT.
4. 3D-bioprinting technology used to represent the complex structure of brain TME.
5. Novel therapies arising from studies of the brain TME in 3D “invitro”
Keywords:
The Tumor Microenvironment in Pediatric Brain Cancer
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
Primary malignant brain tumors (PMBT) are among the most extensively diagnosed tumors in
children throughout the world. They comprise many histological subcategories and are the
principal cause of cancer related death in children from birth to adolescence. The exclusive biology of the brain and its microenvironment are significant common features of this assorted group of diseases. Their complexity represents an additional degree of difficulty in understanding the fundamental biological processes and development of new effective therapies.
Therefore, in the effort to identify new therapeutic targets, the PMBT tumor microenvironment (TME) remains to be the top research interest. The TME in PMBT changes with the disease progression, and its composition can adapt under the pressure of treatment such as surgical resection, radiotherapy or chemotherapy. Moreover, the TME is central to tumorigenesis, tumor expansion and metastasis development. The TME is very complex containing not only tumor cells but also several types of supporting cell types (activated fibroblasts, blood vessels, penetrating immune cells and extracellular matrix), additional cells, hormones and inflammatory responses. Therefore, deep understanding of the TME represents an essential aspect in the prevention, diagnosis and treatment of those tumors.
Over the decades the community of scientists studied the PMBT TME by co-culturing tumor cells with external immune cells using the common 2D “invitro” models and/or humanized mouse models, such as, genetically engineered mouse models (GEMM) and Patient-derived xenografts (PDX). Unfortunately, they found many limitations in preclinical drug testing and addressing mechanism of tumorigenesis.
To address these limitations, 3D “invitro” models (organoids) emerged as newly developed
technique to connect the gap between 2D systems and animal models. In fact, organoid
technologies are able to resemble the cancer tissue architecture in more authentic way,
recapturing both the tumor cells and the stromal matrix of the tumor microenvironment by
using human cells. Moreover, organoid models can replace the use of mice while allowing
scientists to have more direct access to the cellular processes in brain tissue. In addition,
organoid models are particularly useful for the study of cell-cell interactions, tumor invasion,
cellular migration and tumor-immune interactions.
Despite all the advantages organoid technologies represents, the challenge still remains to
authentically mimic the TME of brain tumors. Since naïve organoid are lacking immune cell and
vasculature to study TME, 3D “invitro” tumor models can be designed to be equipped with
these features by forming a chimera called “assembloid”. The characteristics of 3D “invitro”
tumor models can be also adapted to the specific applications purpose: organoid/immune cell
co-culture, air liquid interface, 3D microfluidic and 3D-Bioprintig models.
This research topic aims to provide an overview of newly developed 3D “invitro” preclinical
models designed to study brain tumor-immune system interactions as well as the latest
advancements of brain cancer immunotherapy.
This may include but are not limited to the following sub-topics:
1. Methodology to derive brain TME using both patient derived organoid and induced
pluripotent stem cell (iPSC) brain organoid.
2. Methodology using 3D “invitro” models to study the interaction between PMBT TME
and brain microenvironment.
3. Methodology using 3D “invitro” models to study the immune cells invasion of PMBT.
4. 3D-bioprinting technology used to represent the complex structure of brain TME.
5. Novel therapies arising from studies of the brain TME in 3D “invitro”
Keywords:
The Tumor Microenvironment in Pediatric Brain Cancer
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.