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Microbes & Immunity Characterizing low-grade CNS tumors

rare and typically undiagnosed). Despite the limited sample Taken together, our findings support a proliferation–
size, our investigation revealed distinct patterns of cellular invasion dichotomy with associated angiogenic
organization, proliferative potential, and tissue architecture. implications among low-grade CNS tumors. Based
These features were closely associated with biological on the molecular profiles observed, we propose that
behavior and carry significant prognostic implications. Our combination therapy targeting both MMP activity and
findings highlight the critical need for enhanced molecular neo-vasculogenesis may enhance treatment efficacy
stratification strategies for low-grade CNS tumors. Such in low-grade spinal ependymoma. Similarly, dual
approaches could improve prognostic accuracy and guide inhibition of cell proliferation and neo-vasculogenesis
therapeutic decisions. This preliminary investigation may offer therapeutic benefits in low-grade astrocytic
suggests an emerging pattern that may support prognostic tumors. These approaches hold promise for preventing
assessment in low-grade CNS tumors. malignant progression while minimizing off-target
cytotoxic effects.
Immunohistochemical and flow cytometric
analyses revealed that neoplastic proliferation in WHO Our previous investigations demonstrated a progressive
grade II diffuse astrocytomas – as quantified by GFAP accumulation of both brain-resident microglia and
immunoreactivity and Ki-67 index – demonstrated infiltrating macrophages across the malignancy spectrum
strong correlations with tumor cell proliferative activity from WHO grade II to grade IV astrocytomas. These myeloid
and patient median overall survival. Complementary cell populations play key roles in orchestrating extracellular
22
demographic analyses conducted in South Indian matrix remodeling, which correlates directly with patient
28
populations corroborate these findings, demonstrating morbidity indices. In the present study, quantitative analysis
statistically significant associations between tumor revealed the highest density of SG-stained, electron-dense
proliferative capacity and clinical outcomes. Although microglia and macrophages in meningioma specimens,
23
myxopapillary ependymomas comprise approximately compared to astrocytomas and ependymomas. These findings
15% of all intramedullary spinal cord neoplasms and are were further corroborated through immunophenotyping
traditionally classified as benign lesions with low Ki-67 using CD11b and Iba1 markers.
indices, our molecular profiling paradoxically revealed Previous reports have shown that the extradural
elevated MMP-2 expression at both the cellular and tissue- location and arachnoid-derived origin of meningiomas
architectural levels. This observation indicates an inverse – outside the constraints of the BBB – facilitate immune
correlation between proliferation and invasive potential, cell infiltration. In particular, meningiomas overexpress
revealing a critical paradigm in CNS tumor biology. MMPs monocyte chemoattractant protein-1 (MCP-1), leading
orchestrate extracellular matrix degradation, facilitate to the accumulation of tumor-associated macrophages
basement membrane disruption, and promote tumor cell of monocytic lineage and CD8 tumor-infiltrating
+
invasion and potential metastasis. Previous investigations lymphocytes. These immune cell populations are
have documented significant correlations between frequently associated with peri-tumoral edema,
elevated MMP-2 and MMP-14 expression levels across reflecting the complex interplay between tumor-
WHO grade I–III ependymomas and enhanced invasive secreted chemokines and vascular permeability factors.
behavior, which in turn correlate with poorer patient Conversely, the relatively sparse CD11b cell populations
+
survival outcomes. 24 observed in low-grade astrocytomas are consistent
Our comparative analysis of VEGFR2 expression, with the preserved integrity of the BBB. Tight junction
reflecting neoangiogenic activity, revealed heterogeneous proteins, such as claudin-5, occludin, and zonula
patterns in myxopapillary ependymomas. These patterns occludens-1 help maintain BBB selectivity, thereby
suggest the presence of focal angiogenic switching in restricting the trans-endothelial migration of circulating
areas of gross total resection, despite the typically low monocytes and other peripheral immune effector cells
29,30
proliferative indices observed. The angiogenic switch at early stages of tumor development. This barrier
is governed by complex regulatory networks involving function, coupled with the typically low expression
growth factor signaling pathways (e.g., epidermal growth of MCP-1, limits peripheral monocyte recruitment.
factor, platelet-derived growth factor, and transforming Instead, these tumors demonstrate predominant
+
growth factor) and tissue inhibitors of metalloproteinases activation of brain-resident Iba1 microglia, which
modulation, which are influenced by tumor cells, stromal contribute to tumor progression through the evolving
31,32
fibroblasts, infiltrating macrophages, and other immune tumor–immune synapse.
cells. These elements collectively regulate MMP expression The differential abundance and spatial organization of
and VEGFR2-mediated signaling cascades. 25-27 resident microglia versus infiltrating macrophages within

Volume 2 Issue 3 (2025) 139 doi: 10.36922/MI025190040