Immunoregulation and inflammation in glioblastoma: brain tumors
as neuroinflammatory diseases
Inflammation is an integral component of cancer pathology, contributing
to carcinogenesis and tumor progression. One common feature of GBM is
tissue necrosis accompanied by microenvironment inflammation.
Immunosuppressive inflammation with associated necrosis is typical of
GBMs that display higher resistance to therapies and worst prognosis
[16-20]. GBM cells express and secrete immune suppressive chemokines
and cytokines including interleukin-6, interleukin-10, transforming
growth factor (TGF)-β, galectin-1, and prostaglandin-E, which act on
infiltrating immune cells to hijack them by inducing a pro-tumor
cellular phenotype. Thus, a population of non-neoplastic cells
consisting mostly of tumor-associated macrophages, is established in the
tumor site. These immunosuppressive changes enabled by inflammatory
mediators stimulate GBM cell proliferation, migration, angiogenesis, and
resistance to treatment. For example, signaling mediated by CXCR3 and
CCR2 receptors recruit tumor-promoting immune cells such as T cells and
myeloid-derived suppressor cells [16, 21-28]. In GBM cancer stem
cells (CSCs), hypoxic tissue triggers expression of genes of the
inflammatory reparative response [25, 29]. Cytokines such as
interleukin (IL)-1β and TGF-β cooperate to induce inflammatory gene
expression and a proinflammatory phenotype in GBM CSCs, which in turn
facilitates cellular proliferation and migration [30].