Dichotomy in Growth and Invasion From Low to High Grade Glioma Cellular Variants 

Abstract

Glial dysfunction outraging CNS plasticity and integrity results into one of the most dangerous cancer, namely glioma, featuring little median survival period and high recurrence. The hallmark properties of proliferation, invasion and angiogenesis with the infiltrated macrophages in glioma are expected to be tightly coupled or cross-linked, but not definitely related so far. Present study is aimed to find a relationship between this featured quadrangle from lower to higher grades of post-operative glioma tissues and their invading subsets. Elevated Ki67 associated proliferation in lower grades was supported with VEGF dependent angiogenic maintenance which found decrease unlikely in higher grades. In contrast, MMP-2 and 9 associated invasions augmented high in higher grades with dominant presence of CD204+ M2 polarized macrophages and a general increase in global DNMT1 associated methylation. Marked differences found in ECM invading cellular subsets of higher grades showing high proliferative capacity indicating rationally for recurrence, contrasting the nature of gross tumor tissue of same grade. Thus in lower grades the neoplastic lesion is more inclined for its growth while in higher grade more disposed towards tissue wreckage in support with cellular environmental milieu whereas the cellular variants and subsets of invaded cells showed different trends. Therefore, some operational dichotomy or coupling among cellular variants in glioma is active in determining its low to high grade transition and aggressive progression.

Immunosuppressive cells in oncolytic virotherapy for glioma: challenges and solutions

“…The predominant phenotype of tumor-associated macrophages (TAMs) in the tumor microenvironment during glioma onset and early stages remains unclear (Kennedy et al, 2013). Nevertheless, studies indicate that M2 TAM infiltration increases with glioma progression (Mahlbacher et al, 2018;Yin et al, 2020;Ghosh et al, 2022). Glioma cell proliferation, including glioma stem cells (Yi et al, 2011), results in the secretion of cytokines and chemokines such as MIC-1, periostin, IL-33, and MCP-1 (Wu et al, 2010;Zhou et al, 2015;Roesch et al, 2018;De Boeck et al, 2020), which recruit blood-borne monocytes and macrophages to the tumor site, polarizing them into M2 TAMs.…”