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Microbes & Immunity Characterizing low-grade CNS tumors

proliferation, and pro-tumorigenic M2 polarization. In must be incorporated at the early stages of clinical decision-
addition, microglial repolarization strategies – employing making.
CD40 agonists and/or STAT6 pathway inhibitors – may
facilitate phenotypic switching from pro-tumorigenic M2 to 5. Conclusion
anti-tumorigenic M1 activation states, thereby restraining The study of low-grade CNS tumor samples from a
transformation to higher-grade malignancies. 35,36 hospital-based population revealed a non-linear and
In another aspect of the present study, DNMT1 heterogeneous biological landscape (Table 1). The
expression across low-grade CNS tumor subtypes pathophysiological dynamics observed in WHO grade II
revealed the highest immunoreactivity in WHO grade II diffuse astrocytomas and myxopapillary ependymomas –
astrocytoma specimens, followed by intermediate levels particularly the inverse correlations between proliferative
in ependymomas. Non-glial meningiomas demonstrated capacity, invasive potential, and neoangiogenic activity
moderate DNMT1 expression, suggesting distinct – highlight the necessity of multimodal therapeutic
epigenetic regulatory mechanisms across tumor types. approaches. These findings suggest that targeting
In our previous research, we observed a general trend of interdependent oncogenic pathways simultaneously may
increasing epigenetic perturbation with higher glioma be more effective than conventional single-agent strategies.
grades. However, a comprehensive analysis of epigenetic For low-grade ependymomas, the strategic combination
alterations in post-operative CNS tumor samples across of MMP inhibitors with anti-angiogenic agents could
different subtypes remains largely unexplored and may synergistically disrupt the invasion–angiogenesis axis
offer prognostic benefits. 37,38 The present study highlights while minimizing the cytotoxic effects associated with anti-
the need for further rigorous investigations involving proliferative therapies. In contrast, patients with low-grade
epigenomic profiling of grade-specific CNS neoplasms. astrocytomas may benefit from the use of anti-proliferative
Such studies could provide meaningful prognostic insights agents, such as temozolomide in combination with
and facilitate the identification of novel therapeutic targets, therapies tailored to their unique molecular characteristics.
including DNMT inhibitors, histone deacetylase (HDAC) These could include CSF1/CSF1R pathway antagonists or
+
inhibitors, O6-methylguanine-DNA methyltransferase microglial repolarization agents targeting Iba1 microglial
(MGMT) inhibitors, and isocitrate dehydrogenase activity, anti-angiogenic therapies, and/or epigenetic
inhibitors. These agents may block malignant reprogramming agents, such as DNMT inhibitors,
transformation through epigenetic reprogramming while MGMT inhibitors, and HDAC inhibitors. In low-grade
+
reducing therapeutic resistance and minimizing off-target meningiomas, where CD11b macrophage infiltration
side effects. 39,40 is facilitated by their extradural location and absence of
BBB constraints, immunotherapeutic interventions may
In summary, histopathological evaluation alone is hold particular promise, such as mTOR inhibitors (e.g.,
insufficient for guiding anti-neoplastic treatment strategies. everolimus), CDK4/6 inhibitors, anti-invasive agents, and/
Prognostic success lies in understanding the functional or epigenetic modifiers depending on the minute biological
potential of tumor cells and their microenvironmental properties of the tumor and physiological tolerance of the
interactions. Therefore, molecular characterizations at the patients. Overall, this preliminary investigation suggests
cellular and tissue levels are indispensable for revealing that several key hallmarks of cancer – proliferation,
hallmark tumor features, including proliferation, invasion, invasion, angiogenesis, and immune cell infiltration – may
metastasis, neo-vasculogenic potency, and immune cell manifest distinctly even at early tumor grades, depending
infiltration. 41 on CNS tumor subtype. Recognizing and addressing
Integrating cellular and molecular data with these subtype-specific patterns is essential for advancing
histopathological assessment is thus crucial for the rational personalized therapeutic strategies and optimizing clinical
design of effective anti-cancer treatment regimens. These outcomes in patients with low-grade brain tumors.
findings underscore the importance of molecular and Acknowledgments
genetic tumor characterization, as emphasized in several
recent studies. 10,42,43 Moreover, they highlight the need to The authors acknowledge Prof. S.N. Ghosh at the
examine inter- and intra-tumoral cellular organization Neurosurgery Unit, Bangur Institute of Neurosciences
within the CNS microenvironment – a highly influential (BIN), Institute of Post Graduate Medical Education
factor influencing tumor progression and dissemination, and Research (IPGME&R), Kolkata, for helping in the
even in low-grade lesions. To improve outcomes for collection of post-operative tumor samples, and Prof.
patients with CNS tumors, including prolonged survival Uttara Chatterjee of Pathology Department of IPGME&R
and enhanced quality of life, such diagnostic advancements for identifying and grading tumor samples.

Volume 2 Issue 3 (2025) 141 doi: 10.36922/MI025190040