Impaired B cell immunity in acute myeloid leukemia patients after chemotherapy

Abstract

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

Immune cell repertoires in breast cancer patients after adjuvant chemotherapy

“…The loss of vaccine-specific antibody responses upon B cell depletion is also well described in studies on the effects of rituximab (CD20 depletion therapy) in rheumatoid arthritis, in which patients treated with rituximab display significantly reduced antibody titers and weaker responses to influenza vaccination than untreated controls (31)(32)(33). Notably, AML patients demonstrated significant reduction in somatically hypermutated sequences in the B cell repertoire close to the end of chemotherapy treatment that slowly increased with time after the end of treatment (34), indicative of an initial loss and slow rebound of high-affinity memory B cell responses. The short-term loss of multiple memory B cell subpopulations that, in our study, recovered by 3 years after chemotherapy similarly indicates that memory B cell regeneration occurs via naive B cells converting to memory upon antigen exposure and not memory cells clonally expanding to fill the depleted niche.…”

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“…Patients with myeloid malignancies are known to have poor humoral responses to vaccination despite relatively preserved T cell immunity (33). At the time of diagnosis, the average percentage of B lymphocytes was 1.91 +/− 1.88% of total nucleated compared to a range reported for healthy donors of 6.46 +/− 4.76% (34).…”

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“…And in ammation was associated with immune activation [18]. Myeloid leukocyte activation may activate B cells [19] and improve the tumor microenvironment to make it sensitive to PD-1 agents [20]. Take above all, these gene characteristic maybe in uence the patients response to PD-1 therapy.…”