Immune checkpoint inhibitors reverse T-cell functional suppression in the bone marrow of a subset of AML patients

Abstract

Abstract Acute Myeloid Leukemia is a blood cancer with poor prognosis despite decades of therapeutic development. Immune checkpoint inhibitors (ICIs) have been shown to be effective in many cancers, but their utility in AML has not been clearly established. To better understand the immune landscape of the AML microenvironment, we performed immunophenotyping on fresh bone marrow cells from AML patients using mass-spec based flow cytometry. In addition, we performed functional assays to evaluate T-cell proliferative capacity and determine whether AML bone marrow T cells can be modified by ICI treatment. Sixty two bone marrow samples from patients with AML were analyzed. We performed T-cell stimulation assays to measure proliferation and cytokine production in the presence and absence of ICIs. Samples were sub-categorized as being proliferators or non-proliferators based on the percent of T-cell division in response to TCR stimulation. Phenotypic analysis showed proliferation status correlated with a specific T-cell profile. Additionally, within the non-proliferator group, 70% overcame immune suppression and responded to at least one of the ICIs tested. In conclusion, we show that T-cell dysfunction is present in a subset of patients with AML. Nonetheless, this suppression can be reversed by ICIs in many cases, supporting the use of ICIs in AML therapy.