Radiation induces iatrogenic immunosuppression by indirectly affecting hematopoiesis in bone marrow

Vaishali Kapoor, Andrea Collins, Kaylan Griffith, Subhajit Ghosh, Nathan Wong, Xiaowei Wang, Grant Challen, Joseph Krambs, Dan Link, Dennis E. Hallahan, Dinesh Thotala

Research output: Contribution to journalArticle

Abstract

The immune system plays a vital role in cancer therapy, especially with the advent of immunotherapy. Radiation therapy induces iatrogenic immunosuppression referred to as radiation-induced lymphopenia (RIL). RIL correlates with significant decreases in the overall survival of cancer patients. Although the etiology and severity of lymphopenia are known, the mechanism(s) of RIL are largely unknown. We found that irradiation not only had direct effects on circulating lymphocytes but also had indirect effects on the spleen, thymus, and bone marrow. We found that irradiated cells traffic to the bone marrow and bring about the reduction of hematopoietic stem cells (HSC) and progenitor cells. Using mass cytometry analysis (CyTOF) of the bone marrow, we found reduced expression of CD11a, which is required for T cell proliferation and maturation. RNA Sequencing and gene set enrichment analysis of the bone marrow cells following irradiation showed down-regulation of genes involved in hematopoiesis. Identification of CD11a and hematopoietic genes involved in iatrogenic immune suppression can help identify mechanisms of RIL.

Original languageEnglish
Pages (from-to)1681-1690
Number of pages10
JournalOncotarget
Volume11
Issue number19
DOIs
StatePublished - May 12 2020

Keywords

  • Lymphopenia
  • Mass cytometry RNA sequencing
  • Radiation

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