Specific T-cell immune responses against colony-forming cells including leukemic progenitor cells of AML patients were increased by immune checkpoint inhibition

Enhanced stimulation of antigen‐specific immune responses against nucleophosmin 1 mutated acute myeloid leukaemia by an anti‐programmed death 1 antibody

“…We have previously shown that the immune checkpoint inhibitor PD‐1 can work in combination with peptide‐directed approaches in AML to inhibit LPC/LSC 14 . In this study we showed that 87% of NPM1 mut AML patients had immune responses against at least one LAA and 60% of patients against all four LAA (NPM1 mut , PRAME P300, RHAMM R3, WT1) studied.…”

“…We have previously demonstrated the potential of several leukaemia-associated antigens (LAA; preferentially expressed antigen in melanoma [PRAME -P300], Wilms' tumour 1 [WT1], receptor for hyaluronan-mediated motility (RHAMM -R3) and the mutation specific nucleophosmin1 [NPM1]), which is found in nearly one-third of newly diagnosed patients, 13 can generate T cell-specific immunogenic responses against leukaemic progenitor and stem cells. 14 NPM1 is the most common genetic alteration in adults with AML, 15 causing distinct biological and clinical features. NPM1 is a high conserved nucleo-cytoplasmic shuttling protein, mutations in which cause aberrant cytoplasmic dislocation which led the World Health Organization (WHO) to recognize AML patients with a NPM1-mutation as a distinct entity.…”

Characteristics and mechanisms to control a COVID‐19 outbreak on a leukemia and stem cell transplantation unit

“…A possible explanation could be that in hematological patients a COVID‐19 infection might set off slowly, as the impaired immune system is unable to build up an immediate strong response. In acute leukemia, especially after allogeneic stem cell transplantation, immune reactions against immunogenic antigens like viral antigens but also other immunogenic antigenic structures, are weaker and differ in quality compared to those of healthy controls 23–25 . Intensive mouthwashes, medication or other unknown factors could also explain a longer incubation period in leukemia patients.…”

Neoantigen-Specific T-Cell Immune Responses: The Paradigm of NPM1-Mutated Acute Myeloid Leukemia

“…Consistently, the PARP1 inhibitor olaparib elevated PD-L1 expression, arguing for potential combinatorial therapeutic strategies to enhance the efficacy of ICPIs, at least in this breast cancer subtype [72]. Furthermore, Greiner et al, investigated the influence of nivolumab and anti-CTLA4 antibody ipilumumab on specific immune response to several LAA, namely PRAME, RHAMM, WT1, and #3 peptide from NPM1-mutated protein, by specific T cells, stimulated from 12 AML patients, including five cases harboring NPM1 mutations, against leukemic myeloid blasts and colony-forming cells including leukemic progenitor cells (CFC/LPC) [73]. In functional immunoassays using AML cell lines or primary HLA-A2-positive patient samples, the authors detected specific LAAdirected immune responses against CFC/LPC, which were significantly increased by the addition of nivolumab to CTL cultures, whereas no effect was observed when ipilimumab was added.…”

“…Additionally, the combination of nivolumab and ipilimumab did not improve the inhibitory effect in cell colony growth compared to nivolumab alone. The anti-PD1stimulated cytotoxic responses correlated to PD-L1 expression on leukemic cells, especially on progenitor cells [73]. The same authors, in a larger cohort of 15 NPM1-mutated and 15 NPM1 wild-type AML patients, analyzed the influence of anti-PD1 on antigen-specific immune responses exerted by allogeneic CTLs against CFC/LPC in functional T-cell assays and colony-forming immunoassays [74,75].…”