Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy

Journal of Translational Medicine

Research

Rongye Shi¹  Jinguo Chen¹  Yuri Kotliarov¹  Huizhi Zhou¹  Angelique Biancotto¹  Foo Cheung¹  Lisa King²  Hana Golding²  Jody Manischewitz²  Kimberly Noonan³  Ivan M. Borrello³  B. Douglas Smith³  Gabrielle Prince³  Meghali Goswami⁴  Christopher S. Hourigan⁴  Susan Moir⁵  Lela Kardava⁵  Brian H. Santich⁵  Lauren M. Kunz⁶ 

[1] Center for Human Immunology, Autoimmunity and Inflammation, National Institutes of Health, Bethesda, MD, USA;Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA;Johns Hopkins University, Baltimore, MD, USA;Myeloid Malignancies Section, Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Drive Room 10CRC 5-5216, 20814-1476, Bethesda, MD, USA;National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA;Office of Biostatistics Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA;

关键词: Adaptive immunity;    Leukemia;    B-cells;    T-cells;    Influenza vaccination;    Immunotherapy;   

DOI  :  10.1186/s12967-017-1252-2

 received in 2017-05-18, accepted in 2017-06-21,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundChanges in adaptive immune cells after chemotherapy in adult acute myeloid leukemia (AML) may have implications for the success of immunotherapy. This study was designed to determine the functional capacity of the immune system in adult patients with AML who have completed chemotherapy and are potential candidates for immunotherapy.MethodsWe used the response to seasonal influenza vaccination as a surrogate for the robustness of the immune system in 10 AML patients in a complete remission post-chemotherapy and performed genetic, phenotypic, and functional characterization of adaptive immune cell subsets.ResultsOnly 2 patients generated protective titers in response to vaccination, and a majority of patients had abnormal frequencies of transitional and memory B-cells. B-cell receptor sequencing showed a B-cell repertoire with little evidence of somatic hypermutation in most patients. Conversely, frequencies of T-cell populations were similar to those seen in healthy controls, and cytotoxic T-cells demonstrated antigen-specific activity after vaccination. Effector T-cells had increased PD-1 expression in AML patients least removed from chemotherapy.ConclusionOur results suggest that while some aspects of cellular immunity recover quickly, humoral immunity is incompletely reconstituted in the year following intensive cytotoxic chemotherapy for AML. The observed B-cell abnormalities may explain the poor response to vaccination often seen in AML patients after chemotherapy. Furthermore, the uncoupled recovery of B-cell and T-cell immunity and increased PD-1 expression shortly after chemotherapy might have implications for the success of several modalities of immunotherapy.

【 授权许可】

CC BY   
© The Author(s) 2017