Acquired immunity is not essential for radiation-induced heart dysfunction but exerts a complex impact on injury

Rachel A. Schlaak, Anne Frei, Brian L. Fish, Leanne Harmann, Tracy Gasperetti, Jamie L. Pipke, Yunguang Sun, Hallgeir Rui, Michael J. Flister, Benjamin N. Gantner, Carmen Bergom

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish
Article number983
JournalCancers
Volume12
Issue number4
DOIs
StatePublished - Apr 2020

Keywords

  • Cardiac radiation
  • Cardiotoxicity
  • IL-2 receptor gamma knockout
  • Immune-compromised
  • Immuno-oncology
  • Lymphocytes
  • Radiation
  • Radiation-induced heart disease
  • T cells

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