Increased efficacy of dual proinflammatory cytokine blockade on acute GVHD while maintaining GVT effects

Lam T. Khuat, Logan V. Vick, Cordelia Dunai, Craig P. Collins, Shyam K. More, Catherine T. Le, Chien Chun Steven Pai, Kevin M. Stoffel, Emanual Maverakis, Robert J. Canter, Arta M. Monjazeb, Dan L. Longo, Mehrdad Abedi, Eunju Choi, Bruce R. Blazar, Maneesh Dave, William J. Murphy

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a potential curative option for treating a variety of hematologic diseases, but acute and chronic graft-versus-host disease (GVHD) remain major barriers limiting efficacy. Acute gut GVHD occurs with marked increases in proinflammatory cytokines (including TNF and IL-6), which we recently demonstrated was exacerbated in obesity resulting in severe gastrointestinal pathology. Given the pleiotropic and overlapping effects of these 2 cytokines, we assessed the impact of dual TNF and IL-6R blockade on GVHD as well as graft-versus tumor (GVT) effects in different mouse GVHD models. Early administration of combined blockade resulted in greater protection and survival from acute gut GVHD compared with single blockade regimens and even development of later chronic skin GVHD. Importantly, double cytokine blockade preserved GVT effects reinforcing that GVT and GVHD can be delineated and may result in greater efficacy in allo-HSCT.

Original languageEnglish (US)
Pages (from-to)2583-2588
Number of pages6
JournalBlood
Volume138
Issue number24
DOIs
StatePublished - Dec 16 2021

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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