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Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy

Authors :
Foo Cheung
Hana Golding
Lisa King
Ivan Borrello
Lela Kardava
Angelique Biancotto
Meghali Goswami
Gabrielle T. Prince
Lauren M. Kunz
B. Douglas Smith
Kimberly A. Noonan
Yuri Kotliarov
Jinguo Chen
Susan Moir
Rongye Shi
Huizhi Zhou
Christopher S. Hourigan
Brian H. Santich
Jody Manischewitz
Source :
Journal of Translational Medicine, Vol 15, Iss 1, Pp 1-16 (2017), Journal of Translational Medicine
Publication Year :
2017
Publisher :
BMC, 2017.

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. Electronic supplementary material The online version of this article (doi:10.1186/s12967-017-1252-2) contains supplementary material, which is available to authorized users.

Details

Language :
English
ISSN :
14795876
Volume :
15
Issue :
1
Database :
OpenAIRE
Journal :
Journal of Translational Medicine
Accession number :
edsair.doi.dedup.....3f77ae285f1f6dbf629fd1ce12d7afc6