T-cell apoptosis in human glioblastoma multiforme: Implications for immunotherapy

Abstract

We used immunohistochemistry and flow cytometry to assess apoptosis in human glioblastoma multiforme (GBM). Our immunohistochemical study revealed apoptosis of glioma cells expressing glial fibrillary acidic protein and of CD3 + T cells infiltrating GBM. To quantify and phenotype the apoptotic T cells, we performed flow cytometry on lymphocytes separated from GBM. The cells were stained with annexin-V-FLUOS/propidium iodide to identify apoptosis. We found that high proportions of both the CD4 + and CD8 + T cells were apoptotic. In particular, we found that T cells expressing Fas ligand (Fas-L, CD95L) were eight times more vulnerable to apoptosis than those not expressing Fas-L, which suggests that the Tcell apoptosis is induced by overactivation of the T-cell receptor, possibly in the absence of appropriate costimulation. Our results have implications for the design of immunotherapies for GBM.

Do Cancer Stem Cells have an Immunomodulatory Role Different from the Bulk of Tumor Cells?

“…Like many other type of cancer, the glioma microenvironment become immune suppressive where primed CD8+ cytotoxic T-cells become inhibited or induced to become apoptotic and thus cannot execute their function [57,58]. In addition, there is increased recruitment of other immune suppressive cells like FOXP3+ regulatory T-cells [59].…”

Results of a phase I dendritic cell vaccine trial for malignant astrocytoma: potential interaction with adjuvant chemotherapy

“…6 Our recent work has shown that these cells undergo apoptosis at a high rate. 7 Dendritic cells (DCs) represent a subgroup of white blood cells that are central to the coordination of adaptive immunity owing to their role as professional antigen-presenting cells. They are capable of presenting antigens together with major histocompatibility complex (MHC) I and II molecules 8,9 and as such can stimulate Th4 helper cells as well as cytotoxic T cells.…”

Extracellular Matrix of Glioblastoma Inhibits Polarization and Transmigration of T Cells: The Role of Tenascin-C in Immune Suppression

“…9), supporting the idea that some types of tumors may suppress local immune function by using ECMs to impair lymphocyte infiltration. Our findings provide a plausible explanation at the molecular level to explain why CD3 + T lymphocytes were less frequently observed in glioma tumor nodules but scattered throughout the parenchyma (45,46). Understanding the mechanisms of lymphocyte migration and how they are modulated by a tumor matrix will illuminate new targets for boosting immune surveillance against tumors.…”