CAR-T cell therapy causes inflammation by IL-1 which activates inflammatory cytokine mast cells: anti-inflammatory role of IL-37

J Biol Regul Homeost Agents. 2019 Nov-Dec;33(6):1981-1985. doi: 10.23812/EditorialCaraffa.

Abstract

Chimeric antigen receptor (CAR) T cells are genetically modified T cells that act against cancer. When CAR-T cells are administered they can trigger inflammatory cytokines and increase toxicity. Interleukin (IL)-1 is the classic cytokine that mediates inflammatory reactions including those that occur in CAR-T-cell therapy. IL-1 also induces IL-33 in mast cells (MCs), amplifying the allergic reaction. IL- 37 (ILF7) is an IL-1 family member which binds IL-18 receptor alpha (IL-18Rα) chain and suppresses innate and acquired immunity. IL-37 is an anti-inflammatory cytokine which inhibits pro-inflammatory cytokines including IL-1 and IL-33. Here, we hypothesize that inflammation and toxicity generated in tumor CAR-T therapy could be inhibited by IL-37, contributing to an improvement in the treatment of tumors with CAR-T therapy.

Keywords: CAR-T therapy; chimeric antigen receptor; cytokines; mast cells.

Publication types

  • Editorial

MeSH terms

  • Cell- and Tissue-Based Therapy
  • Humans
  • Immunotherapy, Adoptive*
  • Inflammation / immunology*
  • Interleukin-1 / immunology*
  • Interleukin-33 / immunology
  • Mast Cells / cytology*
  • Receptors, Chimeric Antigen*

Substances

  • IL33 protein, human
  • IL37 protein, human
  • Interleukin-1
  • Interleukin-33
  • Receptors, Chimeric Antigen