Glioma cells display complex cell surface topographies that resist the actions of cytolytic effector lymphocytes.
Gliomas are invasive cancers that resist all forms of attempted therapy. Immunotherapy using Ag-pulsed dendritic cells has improved survival in some patients. We present evidence that another level of complexity may also contribute to lack of responses by the lymphocytes toward gliomas. Atomic force microscopy of four different glioma types-human U251 and rat T9 and F98 glioma cells, including freshly isolated human glioblastoma multiforme neurosphere cultures (containing "stem cell-like cells")-revealed a complex surface topography with numerous microvilli and filopodia. These structures were not found on other cell types. Electron microscopy and immunofluorescence microscopy of glioma cells confirmed that microvilli are present. U251 cells with microvilli resisted the cytolytic actions of different human effector cells, (lymphokine-activated killer cells, γδ T cells, conventional CTLs, and chimeric Ag-receptor-redirected T cells) better than their nonmicrovilli-expressing counterparts. Killer lymphocytes released perforin, which was detected within the glioma's microvilli/filopodia, indicating these structures can receive the cytolytic effector molecules, but cytotoxicity is suboptimal. Air-dried gliomas revealed nodes within the microvilli/filopodia. The microvilli that penetrated 0.4-μm transwell chamber's pores resisted the actions of CTLs and physical damage. Those nodelike structures may represent a compartmentalization that resists physical damage. These microvilli may play multiple roles in glioma biology, such as invasion and resistance to lymphocyte-mediated killing.
Hoa
Neil
N
Pathology and Laboratory Medicine Service, Department of Diagnostic and Molecular Medicine Health Care Group, VA Long Beach Healthcare System, Long Beach, CA 90822, USA.
Ge
Lisheng
L
Kuznetsov
Yurii
Y
McPherson
Alex
A
Cornforth
Andrew N
AN
Pham
Jimmy T H
JT
Myers
Michael P
MP
Ahmed
Nabil
N
Salsman
Vita S
VS
Lamb
Lawrence S
LS
Bowersock
Joscelyn E
JE
Hu
Yuanjie
Y
Zhou
Yi-Hong
YH
Jadus
Martin R
MR
D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000648:ultrastructure*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000276:immunology* / Q000648:ultrastructure*; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D008871:Microvilli / Q000648:ultrastructure; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019139:Tumor Escape