Journal
ONCOIMMUNOLOGY
Volume 7, Issue 4, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2017.1417720
Keywords
Ibrutinib; chronic lymphocytic leukemia B lymphocyte repertoire; chemo-immunotherapy; Immunomonitoring
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Funding
- MD Anderson Cancer Center [CA016672]
- Deutsche Forschungsgemeinschaft (DFG) [110906]
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Using next-generation immunoglobulin (IGH) sequencing and flow cytometry, we characterized the composition, diversity and dynamics of non-malignant B cells in patients undergoing treatment with the Bruton tyrosine kinase (BTK) inhibitor ibrutinib or chemo-immunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR). During ibrutinib therapy, non-malignant B cell numbers declined, but patients maintained stable IGH diversity and constant fractions of IGH-mutated B cells. This indicates partial preservation of antigen-experienced B cells during ibrutinib therapy, but impaired replenishment of the normal B cell pool with naive B cells. In contrast, after FCR we noted a recovery of normal B cells with a marked predominance of B cells with unmutated IGH. This pattern is compatible with a deletion of pre-existing antigen-experienced B cells followed by repertoire renewal with antigen-naive B cells. These opposite patterns in B cell dynamics may result in different responses towards neoantigens versus recall antigens, which need to be further defined.
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