Abstract
The abscopal effect following ionizing radiation therapy (RT) is considered to be a rare event. This effect does occur more frequently when combined with other therapies, including immunotherapy. Here we demonstrate that the frequency of abscopal events following RT alone is highly dependent upon the degree of adrenergic stress in the tumor-bearing host. Using a combination of physiologic, pharmacologic and genetic strategies, we observe improvements in the control of both irradiated and non-irradiated distant tumors, including metastatic tumors, when adrenergic stress or signaling through β-adrenergic receptor is reduced. Further, we observe cellular and molecular evidence of improved, antigen-specific, anti-tumor immune responses which also depend upon T cell egress from draining lymph nodes. These data suggest that blockade of β2 adrenergic stress signaling could be a useful, safe, and feasible strategy to improve efficacy in cancer patients undergoing radiation therapy.
Highlights
The abscopal effect following ionizing radiation therapy (RT) is considered to be a rare event
We previously reported that the standard cool housing temperature mandated for laboratory mice accelerates tumor growth and metastasis and suppresses anti-tumor immunity by subjecting mice to chronic adrenergic stress[28,29]
We began by testing whether the efficacy of ionizing radiation and, the abscopal effect[5,8,38], is influenced by the physiological stress induced by housing mice at the standard (IACUC-mandated) housing temperature
Summary
The abscopal effect following ionizing radiation therapy (RT) is considered to be a rare event. That this abscopal effect is mediated by immune activity is supported by the presence of an increased number of intratumoral CD8+ T cells, especially CD8+ effector/memory T cells (Supplementary Fig. 1c middle and right) in the contralateral, non-irradiated tumors of mice housed at TT.
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