B cell deficiency in patients with relapsed and refractory acute myeloid leukemia.

Abstract

Immune checkpoint inhibition for the treatment of acute myeloid leukemia (AML) has been investigated clinically but has not yet been shown to be more effective than the standard of care treatment [1]. Tumor-specific autologous T cells expressing inhibitory receptors (iRs) are an inherent foundation to this immunotherapy; thus, a detailed picture of cells infiltrating the tumor microenvironment in AML, i.e., the bone marrow (BM), is warranted [2,3]. In this study, we characterized the frequencies and immunophenotypes of adaptive immune cells in the BM of relapsed or refractory AML (R-AML) patients in tandem with age-matched healthy donors (HD) for better contextualization of immunophenotypic variation in both cohorts. We performed deep immunological profiling using multi-parameter flow cytometry of BM of 10 R-AML and 20 age-matched HD, and considered the frequency, composition and expression of clinically relevant iRs across T and B cell subsets in HD and R-AML. Our group previously assessed the BM of this same HD cohort using single-cell RNA sequencing, mass cytometry and flow cytometry to cross-validate these technological approaches and to develop a reference data set for normal immune cell variation in healthy BM [4].