TY - JOUR
T1 - Mechanisms of immunotherapy resistance
T2 - lessons from glioblastoma
AU - Jackson, Christopher M.
AU - Choi, John
AU - Lim, Michael
N1 - Publisher Copyright:
© 2019, Springer Nature America, Inc.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Glioblastoma (GBM) is the deadliest form of brain cancer, with a median survival of less than 2 years despite surgical resection, radiation, and chemotherapy. GBM’s rapid progression, resistance to therapy, and inexorable recurrence have been attributed to several factors, including its rapid growth rate, its molecular heterogeneity, its propensity to infiltrate vital brain structures, the regenerative capacity of treatment-resistant cancer stem cells, and challenges in achieving high concentrations of chemotherapeutic agents in the central nervous system. Escape from immunosurveillance is increasingly recognized as a landmark event in cancer biology. Translation of this framework to clinical oncology has positioned immunotherapy as a pillar of cancer treatment. Amid the bourgeoning successes of cancer immunotherapy, GBM has emerged as a model of resistance to immunotherapy. Here we review the mechanisms of immunotherapy resistance in GBM and discuss how insights into GBM–immune system interactions might inform the next generation of immunotherapeutics for GBM and other resistant pathologies.
AB - Glioblastoma (GBM) is the deadliest form of brain cancer, with a median survival of less than 2 years despite surgical resection, radiation, and chemotherapy. GBM’s rapid progression, resistance to therapy, and inexorable recurrence have been attributed to several factors, including its rapid growth rate, its molecular heterogeneity, its propensity to infiltrate vital brain structures, the regenerative capacity of treatment-resistant cancer stem cells, and challenges in achieving high concentrations of chemotherapeutic agents in the central nervous system. Escape from immunosurveillance is increasingly recognized as a landmark event in cancer biology. Translation of this framework to clinical oncology has positioned immunotherapy as a pillar of cancer treatment. Amid the bourgeoning successes of cancer immunotherapy, GBM has emerged as a model of resistance to immunotherapy. Here we review the mechanisms of immunotherapy resistance in GBM and discuss how insights into GBM–immune system interactions might inform the next generation of immunotherapeutics for GBM and other resistant pathologies.
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U2 - 10.1038/s41590-019-0433-y
DO - 10.1038/s41590-019-0433-y
M3 - Review article
C2 - 31358997
AN - SCOPUS:85069937645
SN - 1529-2908
VL - 20
SP - 1100
EP - 1109
JO - Nature Immunology
JF - Nature Immunology
IS - 9
ER -