Cyclosporine impact on tolerance induction after allo-HCT

Senjo H, Harada S, Kubota SI, et al. Calcineurin Inhibitor Inhibits Tolerance Induction by Suppressing Terminal Exhaustion of Donor T Cells After Allo-HCT. Blood. 2023; (doi: 10.1182/blood.2023019875).

Researchers may have uncovered the reason why, despite routine prophylaxis, so many allogeneic hematopoietic stem cell transplant (allo-HCT) recipients fail to attain long-term tolerance without development of chronic graft-versus-host disease (GVHD). Scientists know that alloreactive donor T cells quickly differentiate into PD-1+ TIGIT+ terminally exhausted T cells (terminal-Tex) after a transplant. Observations from mouse models of HCT show that differentiation of terminal-Tex is suppressed with post-procedure administration of cyclosporine, a calceneurin inhibitor-based prevention protocol. The treatment induces transitory exhausted T cells (transitory-Tex). Tolerance induction is blocked as a result, allowing chronic GVHD to develop after adoptive transfer of transitory-Tex instead of terminal-Tex into secondary recipients. Transitory-Tex maintained reactivity of donor T cells to PD-1 blockade, which subsequently allowed graft-versus-leukemia function to persist and inhibit leukemia relapse.

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Tags: AlloHCT, GVHD, graft, Allo HCT, graft-versus-host disease, graft-vs-host disease, graft-versus-host

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