Combining Radiotherapy and Immunotherapy: Emerging Preclinical Observations of Lymphocyte Costimulatory and Inhibitory R
A greater understanding of immune system biology has translated into more effective cancer immunotherapeutics. This has prompted exploration of the combination of these agents with other cancer treatments such as radiotherapy, which has also been shown to
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Combining Radiotherapy and Immunotherapy: Emerging Preclinical Observations of Lymphocyte Costimulatory and Inhibitory Receptor Modulation Robert M. Samstein, Sadna Budhu, Taha Mergoub, and Christopher A. Barker
Abstract A greater understanding of immune system biology has translated into more effective cancer immunotherapeutics. This has prompted exploration of the combination of these agents with other cancer treatments such as radiotherapy, which has also been shown to promote antitumor immunity independently. This review will present data from reports of immune modulators and radiotherapy and will discuss common themes and observations. Costimulatory molecules including CD40 and CD134/OX40; glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR), CD137/4-1BB; and inhibitory molecules CD152/ cytotoxic T lymphocyte-associated protein 4 (CTLA4), lymphocyte activation gene 3 (LAG3), programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1), and T cell immunoglobulin and mucin domain 3 (TIM-3) will be discussed. Observations regarding radiotherapy sequencing, dose, and fractionation will also be addressed. We conclude that a strategy combining immune modulation and radiotherapy is rational and holds promise for future successful translation in clinical trials. Keywords Radiotherapy • Radiation • Immunotherapy • Immune checkpoint • CTLA4 • PD-1 • PD-L1 • Abscopal effect • Checkpoint blockade
R.M. Samstein • C.A. Barker (*) Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 275 York Avenue, New York, NY 10065, USA e-mail: [email protected]; [email protected] S. Budhu • T. Mergoub Ludwig Collaborative and Swim Across America Laboratory, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA e-mail: [email protected]; [email protected] © Springer International Publishing Switzerland 2017 P.J. Tofilon, K. Camphausen (eds.), Increasing the Therapeutic Ratio of Radiotherapy, Cancer Drug Discovery and Development, DOI 10.1007/978-3-319-40854-5_7
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R.M. Samstein et al.
Introduction A greater understanding of immune system biology has translated into more effective cancer immunotherapeutics. This has prompted exploration of the combination of these agents with other cancer treatments such as radiotherapy, which has also been shown to promote antitumor immunity independently. This review will present data from reports of immune modulators and radiotherapy and will discuss common themes and observations. Costimulatory molecules including CD40 and CD134/ OX40; glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR), CD137/4-1BB; and inhibitory molecules CD152/cytotoxic T lymphocyteassociated protein 4 (CTLA4), lymphocyte activation gene 3 (LAG3), programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1), and T cell immunoglobulin and mucin domain 3 (TIM-3) will be discussed. Observations regarding radiotherapy sequencing, dose, and fractionation will also be addressed.
Cancer Immunity and
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