Jul 4, 2020

T cell dynamics in chronic lymphocytic leukemia under different treatment modalities

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Anna VardiAnastasia Chatzidimitriou

Abstract

Using next-generation sequencing (NGS), we recently documented T cell oligoclonality in treatment-naive chronic lymphocytic leukemia (CLL), with evidence indicating T cell selection by restricted antigens. Here, we sought to comprehensively assess T cell repertoire changes during treatment in relation to: (i) treatment type [fludarabine-cyclophosphamide-rituximab (FCR) versus ibrutinib (IB) versus rituximab-idelalisib (R-ID)], and (ii) clinical response, by combining NGS immunoprofiling, flow cytometry and functional bioassays. T cell clonality significantly increased at: (i) 3 months in the FCR and R-ID treatment groups, and (ii) over deepening clinical response in the R-ID group, with a similar trend detected in the IB group. Notably, in constrast to FCR that induced T cell repertoire reconstitution, B cell receptor signaling inhibitors (BcRi) preserved pre-treatment clones. Extensive comparisons both within CLL as well as against T cell receptor sequence databases showed little similarity with other entities, but instead revealed major clonotypes shared exclusively by CLL patients, alluding to selection by conserved CLL-associated antigens. We then evaluated the functional effect of treatments on T cells and found that: (i) ...Continue Reading

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Mentioned in this Paper

Clone Cells
Finding
Detected (Finding)
Biological Markers
Chronic Lymphocytic Leukemia
T-Cell Activation
Synapse Assembly
Ibrutinib
Signal Transduction Inhibitor
Clone

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