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Enhanced immunosuppression by therapy‐exposed glioblastoma multiforme tumor cells
Author(s) -
Authier Astrid,
Farrand Kathryn J.,
Broadley Kate W.R.,
Ancelet Lindsay R.,
Hunn Martin K.,
Stone Sarrabeth,
McConnell Melanie J.,
Hermans Ian F.
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29309
Subject(s) - immunosuppression , immunotherapy , glioma , immune system , cancer research , cd8 , radiation therapy , in vivo , chemotherapy , medicine , in vitro , immunology , biology , biochemistry , microbiology and biotechnology
Glioblastoma multiforme (GBM) is a highly malignant brain tumor with an extremely short time to relapse following standard treatment. Since recurrent GBM is often resistant to subsequent radiotherapy and chemotherapy, immunotherapy has been proposed as an alternative treatment option. Although it is well established that GBM induces immune suppression, it is currently unclear what impact prior conventional therapy has on the ability of GBM cells to modulate the immune environment. In this study, we investigated the interaction between immune cells and glioma cells that had been exposed to chemotherapy or irradiation in vitro . We demonstrate that treated glioma cells are more immunosuppressive than untreated cells and form tumors at a faster rate in vivo in an animal model. Cultured supernatant from in vitro ‐treated primary human GBM cells were also shown to increase suppression, which was independent of accessory suppressor cells or T regulatory cell generation, and could act directly on CD4 + and CD8 + T cell proliferation. While a number of key immunosuppressive cytokines were overexpressed in the treated cells, including IL‐10, IL‐6 and GM‐CSF, suppression could be alleviated in a number of treated GBM lines by inhibition of prostaglandin E2. These results reveal for the first time that conventional therapies can alter immunosuppressive pathways in GBM tumor cells, a finding with important implications for the combination of immunotherapy with standard treatment.