In vitro studies on the cell-mediated immune response to human brain tumors. II. Leukocyte-induced coats of glycosaminoglycan increase the resistance of glioma cells to cellular immune attack.

Abstract

We have examined the ability of cultured human glioma cells to elicit allogeneic cytolytic lymphocyte responses in vitro in order to delineate properties of glioma cells that may contribute to their ability to escape cellular immune attack. When glioma cells were cultured together with allogeneic peripheral blood mononuclear cells (PBMC) in mixed lymphocyte-tumor cultures (MLTC), it was observed that cells from eight of 12 glioma lines were surrounded by clear pericellular "halos," which appeared to impede contact between PBMC and the glioma cells. Enzymatic, histochemical, and immunochemical studies indicated that these halos represented glycosaminoglycan (GAG) coats that contained hyaluronic acid (HA) as a major constituent. Electron microscopic studies demonstrated the presence of many thin microvillous processes spanning the width of the halos. The presence of GAG coats around glioma cells in MLTC reduced the generation of cytolytic T lymphocytes specific for antigens on the glioma cells. Likewise, these cell coats decreased the lysis of glioma cells by cytolytic lymphocytes, once generated. The production of thick coats of GAG by glioma cells was induced by interaction of glioma cells with a nondialyzable factor produced by PBMC in culture. This factor did not cause glioma cells to release increased amounts of HA into the medium, but rather increased the production of HA that remained associated with the glioma cell surface. The formation of thick, protective GAG coats by glioma cells as a result of their interaction with the PBMC-derived factor constitutes a nonspecific suppressor mechanism that may contribute to the ability of this class of human solid tumors to evade cellular immune attack.

Glioblastoma extracellular vesicles influence glial cell hyaluronic acid deposition to promote invasiveness

“…Consistently, studies in which GBM and peripheral blood cells were co-cultured indicated that GBM cells can surround themselves with a halo of HA-rich glycosaminoglycans. 45 Therefore, increased HA expression by surrounding astrocytes might serve as an additional barrier to invading immune cells while simultaneously promoting GBM invasion.…”

Hyaluronic acid as a pulpotomy material in primary molars: an up to 30 months retrospective study

“…Its biophysical properties confer upon HA functions that impact the hydration and biomechanical properties of various tissues, particularly those of the vitreous humor in the eye, the synovial joint uid, and the dermis [10]. Additionally, HA also interacts with extracellular macromolecules and HA-binding proteoglycans, such as versican and aggrecan, crucial for the assembly of ECMs and of pericellular glycocalyces, which can function as protective cellular barriers and are essential for the assembly and structure of various tissues [10][11][12][13]. Physiological functions of HA are mediated by molecular interactions with CD44 and RHAMM and other HA-binding proteins [11].…”