Abstract
While radiation therapy (RT) can improve cancer outcomes, it can lead to radiation-induced heart dysfunction (RIHD) in patients with thoracic tumors. This study examines the role of adaptive immune cells in RIHD. In Salt-Sensitive (SS) rats, image-guided whole-heart RT increased cardiac T-cell infiltration. We analyzed the functional requirement for these cells in RIHD using a genetic model of T- and B-cell deficiency (interleukin-2 receptor gamma chain knockout (IL2RG−/−)) and observed a complex role for these cells. Surprisingly, while IL2RG deficiency conferred protection from cardiac hypertrophy, it worsened heart function via echocardiogram three months after a large single RT dose, including increased end-systolic volume (ESV) and reduced ejection fraction (EF) and fractional shortening (FS) (p < 0.05). Fractionated RT, however, did not yield similarly increased injury. Our results indicate that T cells are not uniformly required for RIHD in this model, nor do they account for our previously reported differences in cardiac RT sensitivity between SS and SS.BN3 rats. The increasing use of immunotherapies in conjunction with traditional cancer treatments demands better models to study the interactions between immunity and RT for effective therapy. We present a model that reveals complex roles for adaptive immune cells in cardiac injury that vary depending on clinically relevant factors, including RT dose/fractionation, sex, and genetic background.
Highlights
IntroductionRadiation therapy (RT) is established as a major modality in treating malignancies, with over 50%
Radiation therapy (RT) is established as a major modality in treating malignancies, with over 50%of cancer patients receiving RT
We investigated the consequences of RT treatment understanding how they might contribute to radiation-induced heart dysfunction (RIHD)
Summary
Radiation therapy (RT) is established as a major modality in treating malignancies, with over 50%. While RT is used to treat the tumor, toxic side effects to surrounding normal tissues can occur, and normal tissue radiation exposure increases the potential for acute and/or chronic complications in cancer patients. As cancer therapies continue to improve, the number of cancer survivors continues to grow, adding to the global cancer burden. This concern is amplified in thoracic cancers where protecting the heart is a major concern. The most common RT-induced heart and vascular toxicities, collectively referred to as radiation-induced heart dysfunction (RIHD), include pericarditis, ischemic heart disease, conduction abnormalities, myocardial fibrosis, and dysfunctional valves [2,3,4,5,6]
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