One of the most frequently altered genes in AML is nucleophosmin1 (NPM1), which is frequently linked to a good prognosis. Immunological responses increasingly influenced treatment choices for AML. However, it was unclear how immune checkpoint inhibition functions. For a study, researchers sought to determine the particular immune responses of AML patients to NPM1, PRAME, Wilms’ tumor 1, RHAMM, and 3 additional leukemia-associated antigens (LAA).
Using colony-forming immunoassays and flow cytometry, they examined T cell responses against leukemic progenitor/stem cells (LPC/LSC). In addition, comparing cells from NPM1 mutant and NPM1 wild-type AML patients, they investigated whether immune checkpoint suppression with the anti-programmed death 1 antibody improved the immune response to stem cell-like cells.
Nivolumab, an anti-PD-1 antibody, was reported to enhance the number of LAA-stimulated cytotoxic T cells and to have a cytotoxic impact on LPC/LSC. When the immunogenic epitope was obtained from the area of NPM1 that had been altered, the impact was best against NPM1mut cells and the effects were strengthened by the addition of anti-PD-1.
The results implied that the immune checkpoint inhibitor anti-PD-1 may be used to treat individuals with NPM1 mutant AML and that this treatment, in combination with NPM1-mutation specific directed immunotherapy, may be even more successful for this particular subset of patients.