Tumors are never something to joke around about; they are
dangerous, unpredictable, and they can even be fatal. They can appear nearly
anywhere in the human body, at basically any point in time. In fact, one of the most
dangerous habitats for a tumor is the brain. A complicated and mysterious part
of the human body already, the brain controls almost everything, and a tumor
appearing in this region can be devastating. They are difficult to remove, and
they can have disastrous mental and physical consequences. Even worse, they can
present themselves at any age. This makes children susceptible, and what could
be worse than that? With around 1,500 children diagnosed a year, pediatric
brain tumors are not the most common cause of death in children (1). However,
they are the most common type of pediatric tumor, and they have the highest
mortality rate over all other childhood cancers. Despite its reputation, this
deadly disease has had no improvements regarding treatment methods in the past.
Until recently even, the standard treatment was radiation exposure and
chemotherapy, which were often coupled with horrible, debilitating side effects.
Now, a new form of treatment has been devised due to its tumor specificity –
immunotherapy.
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| "Types of Brain and Spinal Cord Tumors in Children." Johns Hopkins Medicine. Johns Hopkins University, Hospital, and Health System, 2013. Web. 10 Dec. 2013. |
Studies have shown that there have
been positive correlations between host immunity and survival rate in children
diagnosed with brain tumors. Still, immunotherapy has demonstrated to be
largely ineffective due to the immunosuppression induced by brain tumors
because it tampers with the immune system-supressing qualities of the exogenous
therapy. Several scientists researched pediatric brain tumor types further,
however, in order to better understand immunophenotypes – the immunological
characteristics – of these tumors. They hoped to shed some light on the subject
in order to be able to better treat these afflicted children and give them more
of a fighting chance.
In
Andrea Griesinger and her colleagues’ study, they measured the phenotype and
frequency of tumor-infiltrating leukocytes in the four most common types of
child brain tumors*(4). They began by surgically taking tumor samples from
forty-two patients at the Children’s Hospital in Colorado; they also took five
non-tumor samples for a control group. Then, the tissue samples were disaggregated and frozen, before
they were eventually suspended, stained, and analyzed via a FACS analysis and a
gene expression analysis (2, 3). The FACS analysis then sorted the variety of
cells into two or more containers based on their fluorescence while the gene
expression analysis quantified the expression levels of certain genes.
In their
results, Griesinger and the other scientists found that the amount of infiltration,
or migration, of certain cells to the tumors heavily depended on the type of
tumor. Myeloid cells were mostly found in pilocytic astrocytomas (PA) or
ependymomas (EPN), for example. These myeloid cell phenotypes were also more
activated in PA and EPN, and the activation markers were higher in prevalence
as well. Similarly, T cells were found to be distributed like myeloid cells,
but they were less common. CD8+ and CD4+ T cells greatly varied between tumor
cell types as well. Overall, however, after analyzing everything in their data
the scientists founds that each type of tumor had a distinctive immunophenotype,
emphasizing the uniqueness of each particular pediatric brain tumor.
Previous
studies have focused primarily on the adult form of glioblastoma (GBM), and
many findings on tumors have taken knowledge from GBM research without
realizing that GBM phenotypes may not be applicable to other tumor types. PA
and EBN display more leukocyte infiltration than any of the other tumors
tested, for example, and medulloblastoma (MED) had far less leukocyte
infiltration than the other tumors. The importance of this information cannot
be lost on the details, however. These infiltrating leukocytes that were
studied signify sources of endogenous cells that can be utilized by the immune
system. This is where the immunotherapy comes in. The three types of
immunotherapies – passive, adoptive, and active – could be utilized for
different types of brain tumors, depending on the levels of certain cells in
the tumors and what phenotypes were more activated and where. Thus, these
findings will hopefully help in figuring out the specifics for treatment of
pediatric brain tumors, improving immunotherapeutic approaches all the while
discouraging the more damaging chemotherapeutic treatment.
*Brain
Tumors Studied: Pilocytic Astrocytoma, Ependymoma, Medulloblastoma, and
Glioblastoma.
Primary
Article:
Griesinger,
Andrea M. et. al. 2013. Characterization of Distinct Immunophenotypes across
Pediatric Brain
Tumor Types. Journal of
Immunology. 191: 4880-4888.
Other
Articles:
4. http://www.cbtf.org/learn/what-brain-tumors-are-common-iImage:
"Types of Brain and Spinal Cord Tumors in Children." Johns Hopkins Medicine. Johns Hopkins University, Hospital, and Health System, 2013. Web. 10 Dec. 2013.
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