Page 208 - Read Online

Buerki et al. Biomarkers in glioma

increased in higher grade tumors, with increased GBM continues to be a catastrophic tumor, with
Treg infiltration indicating a worse prognosis. eventual recurrence and poor survival, in no small
[12]
Furthermore, it has been shown than TILs are enriched part due to tumor-based immunosuppression.
in the mesenchymal molecular GBM subclass, which Immunotherapy is a promising addition to the current
[13]
has also been correlated with improved response to standard of care. The studies highlighted here by
immunotherapy. Han et al. describe a prospective, Alexiou et al. [6,7] emphasize the growing role of
[15]
[14]
single-center series of GBM patients comparing immune cells and antibodies in the understanding
intratumoral infiltration of macrophages and T cells and of both gliomagenesis, glioma progression, and the
corroborating pre-treatment NLR (using a cut-off value development of aggressive and treatment-resistant
of 4) with survival, establishing that serum neutrophil tumor types. They do not identify a causal role for
and lymphocytes levels (and thus the NLR) reflect the certain inflammatory mediators either as protective or
presence of TILs within the tumor milieu. In another tumor-suppressive, but rather begin to pinpoint immune
study by Berghoff et al. a single-center retrospective phenotypes of GBM. Furthermore, they provide easily
[16]
analysis (“Vienna cohort”), improved survival was not measurable biomarkers for immunosuppressive
associated with TIL density (or PD-L1 overexpression), GBM phenotypes, which are prognostic for patient
in contrast the other studies. Routine analysis of TILs survival and are clearly applicable to clinical trials for
is difficult in clinical settings, so it is crucial that the novel immunotherapies. Subsequent work is needed
study of Alexiou et al. [6,7] mirrors the use of serum to correlate these findings to other prognostic GBM
kynurenine and tryptophan levels as another biomarker markers or subtypes (e.g. MGMT promoter methylation,
of the immunosuppressive effect of IDO catabolism in presence of IDH1 mutations, etc.) and imaging
characteristics (e.g. pseudoprogression following both
gliomas, which demonstrated prognostic significance standard treatment and immunotherapy is thought
for OS in a prospective, multi-center observational [20]
trial of GBM patients. [17] Taken together, the work to be an immune-mediated response ). In fact,
immunotherapy-induced changes on neuroimaging
of Alexiou et al., Bambury et al., and Han et al. have been incorporated in to the newest response
[15]
[9]
[6]
elaborate upon the role of TILs in GBM via an easily assessment guidelines (“iRANO” ), but whether
[21]
obtainable, non-invasive, serum biomarker proxy. these serum biomarkers correlate remains unclear. It
These papers reinforce and expand upon the paradigm is equally important to identify any mechanistic role of
that GBM is a lymphocyte-suppressing tumor as well IgE, and also CD4+ Th2 cells, CD4+/CD25+/FoxP3+
as that lymphocyte down-regulation is itself a marker Treg cells, or the IgE-driving cytokines IL-4 and IL-13,
of an aggressive tumor pathology. in the glioma milieu and the promulgation of tumor
immunosuppression. Of further value would also be to
The second article by Alexiou et al., also a expand upon the prognostic findings described here to
[7]
prospective, single-institution observational study of determine if the serum NLR or IgE levels are useful to
patients undergoing surgery for intracranial tumors assess treatment response.
(not limited to GBM), revealed that lower serum
IgE levels in the GBM patients were a prognostic Financial support and sponsorship
marker associated with poorer survival and higher- Nil.
grade in gliomas, although the result was of marginal
significance statistically. IgE levels in gliomas and Conflicts of interest
meningiomas were also significantly lower than in There are no conflicts of interest.
metastatic tumors. This supports prior work on IgE
and allergies in the development of malignancies. For Patient consent
example, in a large, multi-center, case-controlled study No patient involved.
of self-reported medically-diagnosed allergies, there
was an inverse relationship between allergies and Ethics approval
gliomas. Furthermore, this association was incidence This article does not contain any studies with human
responsive, the greater number of medically-diagnosed participants or animals.
allergies the lower the glioma risk. A number of
[18]
previous studies also suggest that a general atopy REFERENCES
phenotype rather than a specific allergy type/allergen
is correlated with decreased glioma risk, [18,19] which is 1. Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C,
Wolinsky Y, Kruchko C, Barnholtz-Sloan JS. CBTRUS statistical
consistent with the total serum IgE results discussed report: primary brain and central nervous system tumors diagnosed in
here. Thus, it is not a limitation of Alexiou’s study that the United States in 2008-2012. Neuro Oncol 2015;17 Suppl 4:iv1-62.
allergen-specific IgE antibodies were not elucidated. 2. Lukas RV, Mrugala MM. Pivotal therapeutic trials for infiltrating
Neuroimmunology and Neuroinflammation ¦ Volume 3 ¦ September 26, 2016 199