![]() ![]() Saber,Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission. We thus defined mechanisms of resistance to T cell–mediated antitumor effects after alloBMT and described an immunotherapy approach targeting stem-like memory T cells to enhance antitumor immunity.Ī. Whereas ICI with anti–PD-1 or anti–TIM-3 remained ineffective after PT-Cy, administration of a decoy-resistant IL-18 (DR-18) strongly enhanced GVT effects in both myeloma and leukemia models, without exacerbation of GVHD. Administration of post-transplant cyclophosphamide (PT-Cy) depleted donor T cells with an exhausted phenotype and spared T cells displaying a stem-like memory phenotype with chromatin accessibility present in cytokine signaling genes, including the interleukin-18 (IL-18) receptor. Because of this tumor-independent exhaustion signature, immune checkpoint inhibition (ICI) in myeloma exacerbated graft-versus-host disease (GVHD) without promoting GVT effects. We found that CD8 + T cell exhaustion in bone marrow was primarily alloantigen-driven, with expression of inhibitory ligands present on myeloma but not AML. We developed murine models of alloBMT where the hematological malignancy is either sensitive or resistant (myeloma) to GVT effects. Allogeneic bone marrow transplantation (alloBMT) is the only curative immunotherapy for hematological malignancies due to profound graft-versus-tumor (GVT) effects, but relapse remains the major cause of death. Some hematological malignancies such as multiple myeloma are inherently resistant to immune-mediated antitumor responses, the cause of which remains unknown.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |