Abstract
BackgroundAcute myeloid leukemia (AML), caused by the abnormal proliferation of immature myeloid cells in the blood or bone marrow, is one of the most common hematologic malignancies. Currently, the interactions between malignant myeloid cells and the immune microenvironment, especially T cells and B cells, remain poorly characterized.MethodsIn this study, we systematically analyzed the T cell receptor and B cell receptor (TCR and BCR) repertoires from the RNA-seq data of 145 pediatric and 151 adult AML samples as well as 73 non-tumor peripheral blood samples.ResultsWe inferred over 225,000 complementarity-determining region 3 (CDR3) sequences in TCR α, β, γ, and δ chains and 1,210,000 CDR3 sequences in B cell immunoglobulin (Ig) heavy and light chains. We found higher clonal expansion of both T cells and B cells in the AML microenvironment and observed many differences between pediatric and adult AML. Most notably, adult AML samples have significantly higher level of B cell activation and more secondary Ig class switch events than pediatric AML or non-tumor samples. Furthermore, adult AML with highly expanded IgA2 B cells, which might represent an immunosuppressive microenvironment, are associated with regulatory T cells and worse overall survival.ConclusionsOur comprehensive characterization of the AML immune receptor repertoires improved our understanding of T cell and B cell immunity in AML, which may provide insights into immunotherapies in hematological malignancies.
Highlights
Acute myeloid leukemia (AML), caused by the abnormal proliferation of immature myeloid cells in the blood or bone marrow, is one of the most common hematologic malignancies
We observed a significantly positive correlation between T cell receptor (TCR)/ B cell receptor (BCR) entropy and CDR3s per kilo TCR/BCR reads (CPK) (Additional file 2: Figure S1c). Based on these results and our previous work, we conclude that our approach has sufficient power to recover TCR and BCR complementarity-determining region 3 (CDR3) to evaluate the fraction and diversity of both T and B cells from bulk RNA-seq data, which allowed us to identify the changes of T and B cells between AML and non-tumor samples
We found that pediatric AML with highly expanded IgA1 B cells and adult AML with highly expanded IgA2 B cells, which might represent an immunosuppressive
Summary
Acute myeloid leukemia (AML), caused by the abnormal proliferation of immature myeloid cells in the blood or bone marrow, is one of the most common hematologic malignancies. The standard therapy for AML has been chemotherapy regimens with or without allogeneic hematopoietic stem cell transplantation [2]. Characterizing tumor TCR and BCR repertoires, the CDR3s, is critical to understanding antigen recognition and tumor–immune interactions. Less is known about the immune repertoire changes in hematologic malignancies, and a systematic characterization of both TCR and BCR repertoires in the AML microenvironment is still lacking
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