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Molecular and cellular features of CTLA-4 blockade for relapsed myeloid malignancies after transplantation. | LitMetric

AI Article Synopsis

  • Relapsed myeloid disease after allogeneic stem cell transplantation is difficult to treat, but immune checkpoint blockade with drugs like ipilimumab shows promise in enhancing the graft-versus-leukemia (GVL) response.
  • A study was conducted where patient biopsies and blood samples were analyzed, revealing that ipilimumab treatment led to increased activation and infiltration of CD8+ T-cells in the local tumor environment.
  • Patients who responded well to ipilimumab showed significant changes in T-cell populations, increased markers of T-cell activation, and higher levels of inflammatory chemokines in their blood, indicating that ipilimumab effectively alters the immune response in a beneficial way.

Article Abstract

Relapsed myeloid disease after allogeneic stem cell transplantation (HSCT) remains largely incurable. We previously demonstrated the potent activity of immune checkpoint blockade in this clinical setting with ipilimumab or nivolumab. To define the molecular and cellular pathways by which CTLA-4 blockade with ipilimumab can reinvigorate an effective graft-versus-leukemia (GVL) response, we integrated transcriptomic analysis of leukemic biopsies with immunophenotypic profiling of matched peripheral blood samples collected from patients treated with ipilimumab following HSCT on the Experimental Therapeutics Clinical Trials Network 9204 trial. Response to ipilimumab was associated with transcriptomic evidence of increased local CD8+ T-cell infiltration and activation. Systemically, ipilimumab decreased naïve and increased memory T-cell populations and increased expression of markers of T-cell activation and costimulation such as PD-1, HLA-DR, and ICOS, irrespective of response. However, responding patients were characterized by higher turnover of T-cell receptor sequences in peripheral blood and showed increased expression of proinflammatory chemokines in plasma that was further amplified by ipilimumab. Altogether, these data highlight the compositional T-cell shifts and inflammatory pathways induced by ipilimumab both locally and systemically that associate with successful GVL outcomes. This trial was registered at www.clinicaltrials.gov as #NCT01822509.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351891PMC
http://dx.doi.org/10.1182/blood.2021010867DOI Listing

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