Cytokine-induced memory-like (CIML) NK cells in myeloid malignancies

Current understanding

Cytokine-induced memory-like (CIML) NK cells are NK cells preactivated with IL-12, IL-15, and IL-18 that acquire enhanced and durable effector function against myeloid blasts. In the post-transplant relapse setting for AML, MDS, and MPN, adoptive transfer of CIML NK cells supported by IL-2 is being explored as a graft-versus-leukemia-augmenting strategy that bypasses T-cell exhaustion and HLA-restriction. Mechanistically this leverages NK-mediated immunosurveillance of malignant myeloid clones, a pathway distinct from JAK-STAT-targeting and checkpoint blockade approaches in MPN.

Evidence log

• 2026-09-01 — Type-I interferon-activated NK cells control polycythemia vera in vivo.: Preclinical demonstration that endogenous, type-I-IFN-activated NK cells selectively kill JAK2V617F-mutant HSPCs provides mechanistic rationale for CIML NK adoptive strategies in MPN, suggesting cytokine-primed NK cells engage a bona fide mutant-HSPC-selective cytotoxicity program rather than nonspecific myeloid clearance. (novelty: 5)
• 2026-06-24 — Chimeric Antigen Receptor T Cell Therapy Redirected to CD4 (CD4CAR)as a Second Line Treatment for Chronic Myelomonocytic Leukemia, CMML.: Cross-connection with cd4-car-t-cell-therapy-cmml: CD4CAR T cells redirected against CD4+ monocytic CMML clones constitute a parallel adoptive cellular immunotherapy strategy to CIML NK cells, sharing the principle of leveraging engineered immune effectors against myeloid malignancy but using antigen-specific HLA-independent CAR engagement rather than cytokine-primed innate NK cytotoxicity. (novelty: 4)
• 2026-06-17 — Preemptive CIML NK Cell Therapy After Hematopoietic Stem Cell Transplantation: Clinical trial testing preemptive post-allo-HSCT infusion of CIML NK cells expanded with IL-2 to prevent relapse in AML, MDS, and MDS/MPN overlap extends the CIML NK strategy from established-relapse salvage into a preemptive relapse-prevention setting. (novelty: 4)
• 2026-06-11 — Elotuzumab for the Treatment of JAK2-Mutated Myelofibrosis: cross-connection with slamf7-immunotherapy-mpn: Both leverage NK-cell-mediated killing of MPN clones — SLAMF7 engagement by elotuzumab activates NK effectors and triggers ADCC, mechanistically converging with CIML NK-cell adoptive strategies on innate immune control of myeloid malignancy. (novelty: 4)
• 2026-05-15 — Identification of MPN-specific Antigens and Anti-MPN TCRs in Myeloproliferative Neoplasm: Parallel effort to identify MPN-specific TCRs frames an HLA-restricted, T-cell-based immunotherapy axis that contrasts with HLA-independent CIML NK approaches but shares the goal of augmenting graft-versus-clone activity. (novelty: 4)

Open questions

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