Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy

Meghali Goswami, Gabrielle Prince, Angelique Biancotto, Susan Moir, Lela Kardava, Brian H. Santich, Foo Cheung, Yuri Kotliarov, Jinguo Chen, Rongye Shi, Huizhi Zhou, Hana Golding, Jody Manischewitz, Lisa King, Lauren M. Kunz, Kimberly Noonan, Ivan M Borrello, B Douglas Smith, Christopher Hourigan

Research output: Contribution to journalArticle

Abstract

Background: Changes 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. Methods: We 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. Results: Only 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. Conclusion: Our 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.

Original languageEnglish (US)
Article number155
JournalJournal of Translational Medicine
Volume15
Issue number1
DOIs
StatePublished - Jul 10 2017

Keywords

  • Adaptive immunity
  • B-cells
  • Immunotherapy
  • Influenza vaccination
  • Leukemia
  • T-cells

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Goswami, M., Prince, G., Biancotto, A., Moir, S., Kardava, L., Santich, B. H., Cheung, F., Kotliarov, Y., Chen, J., Shi, R., Zhou, H., Golding, H., Manischewitz, J., King, L., Kunz, L. M., Noonan, K., Borrello, I. M., Smith, B. D., & Hourigan, C. (2017). Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy. Journal of Translational Medicine, 15(1), [155]. https://doi.org/10.1186/s12967-017-1252-2