Select Antitumor Cytotoxic CD8⁺ T Clonotypes Expand in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib.

ABSTRACT:

Purpose

In chronic lymphocytic leukemia (CLL), the T-cell receptor (TCR) repertoire is skewed and tumor-derived antigens are hypothesized as drivers of oligoclonal expansion. Ibrutinib, a standard treatment for CLL, inhibits not only Bruton tyrosine kinase of the B-cell receptor signaling pathway, but also IL2-inducible kinase of the TCR signaling pathway. T-cell polarization and activation are affected by ibrutinib, but it is unknown whether T cells contribute to clinical response.

Experimental design

High-throughput TCRβ sequencing was performed in 77 longitudinal samples from 26 patients with CLL treated with ibrutinib. TCRβ usage in CD4⁺ and CD8⁺ T cells and granzyme B expression were assessed by flow cytometric analysis. Antitumor cytotoxicity of T

SUBMITTER: Baptista MJ 

PROVIDER: S-EPMC8364883 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature