Supplementary tables and figure legends from Disruption of in vivo Chronic Lymphocytic Leukemia Tumor–Microenvironment Interactions by Ibrutinib – Findings from an Investigator-Initiated Phase II Study

Niemann, Carsten U.; Herman, Sarah E.M.; Maric, Irina; Gomez-Rodriguez, Julio; Biancotto, Angelique; Chang, Betty Y.; Martyr, Sabrina; Stetler-Stevenson, Maryalice; Yuan, Constance M.; Calvo, Katherine R.; Braylan, Raul C.; Valdez, Janet; Lee, Yuh Shan; Wong, Deanna H.; Jones, Jade; Sun, Clare; Marti, Gerald E.; Farooqui, Mohammed Z.H.; Wiestner, Adrian

doi:10.1158/1078-0432.22459316.v1

Supplementary tables and figure legends from Disruption of <i>in vivo</i> Chronic Lymphocytic Leukemia Tumor–Microenvironment Interactions by Ibrutinib – Findings from an Investigator-Initiated Phase II Study

https://doi.org/10.1158/1078-0432.22459316

journal contribution

posted on 2023-03-31, 18:49 authored by Carsten U. Niemann, Sarah E.M. Herman, Irina Maric, Julio Gomez-Rodriguez, Angelique Biancotto, Betty Y. Chang, Sabrina Martyr, Maryalice Stetler-Stevenson, Constance M. Yuan, Katherine R. Calvo, Raul C. Braylan, Janet Valdez, Yuh Shan Lee, Deanna H. Wong, Jade Jones, Clare Sun, Gerald E. Marti, Mohammed Z.H. Farooqui, Adrian Wiestner

<p>Supplementary Table S1: Evaluation of serum cytokine levels on ibrutinib Supplementary Table S2: Evaluation of chemoattractant levels in bone marrow supernatant on ibrutinib supplementary figure legends for supplementary figures S1-S5</p>

Funding

National Heart, Lung, and Blood Institute

Danish Cancer Society

History

Related Materials

1.
DOI - Is supplement to Disruption of in vivo Chronic Lymphocytic Leukemia Tumor–Microenvironment Interactions by Ibrutinib – Findings from an Investigator-Initiated Phase II Study

ARTICLE ABSTRACT

Purpose: Chronic lymphocytic leukemia (CLL) cells depend on microenvironmental interactions for proliferation and survival that are at least partially mediated through B-cell receptor (BCR) signaling. Ibrutinib, a Bruton tyrosine kinase inhibitor, disrupts BCR signaling and leads to the egress of tumor cells from the microenvironment. Although the on-target effects on CLL cells are well defined, the impact on the microenvironment is less well studied. We therefore sought to characterize the in vivo effects of ibrutinib on the tumor microenvironment.Experimental Design: Patients received single-agent ibrutinib on an investigator-initiated phase II trial. Serial blood and tissue samples were collected pretreatment and during treatment. Changes in cytokine levels, cellular subsets, and microenvironmental interactions were assessed.Results: Serum levels of key chemokines and inflammatory cytokines decreased significantly in patients on ibrutinib. Furthermore, ibrutinib treatment decreased circulating tumor cells and overall T-cell numbers. Most notably, a reduced frequency of the Th17 subset of CD4+ T cells was observed concurrent with reduced expression of activation markers and PD-1 on T cells. Consistent with direct inhibition of T cells, ibrutinib inhibited Th17 differentiation of murine CD4+ T cells in vitro. Finally, in the bone marrow microenvironment, we found that ibrutinib disaggregated the interactions of macrophages and CLL cells, inhibited secretion of CXCL13, and decreased the chemoattraction of CLL cells.Conclusions: In conjunction with inhibition of BCR signaling, these changes in the tumor microenvironment likely contribute to the antitumor activity of ibrutinib and may impact the efficacy of immunotherapeutic strategies in patients with CLL. Clin Cancer Res; 22(7); 1572–82. ©2015 AACR.See related commentary by Bachireddy and Wu, p. 1547