Tumoricidal Effects of Activated Macrophages in a Mouse Model of Chronic Lymphocytic Leukemia

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2009 May 21

PMID 19454672

Citations 16

Authors

Qing-Li Wu

Ilia N Buhtoiarov

Paul M Sondel

Alexander L Rakhmilevich

Erik A Ranheim

Affiliations

Soon will be listed here.

Abstract

The Emu-TCL1 transgenic mouse spontaneously develops a CD5(+) B cell lymphoproliferative disorder similar to human chronic lymphocytic leukemia (CLL). Given the ineffectual T cell antitumor responses in this mouse model of CLL, we sought to determine whether combined treatment with anti-CD40 mAb (alphaCD40) and CpG-containing oligodeoxynucleotides (CpG) could exert immunotherapeutic effects. We have previously shown that macrophages activated by sequential ligation of CD40 and TLR9 could become cytotoxic against solid tumor cell lines both in vitro and in vivo. In the current study, we find that alphaCD40 plus CpG-activated macrophages induce tumor B cell apoptosis in vitro and that alphaCD40 plus CpG treatment markedly retards tumor growth in immunodeficient SCID/Beige mice following transplantation of primary tumor B cells. Our results suggest a novel immunotherapeutic strategy for CLL that may be effective even in the face of tumor or chemotherapy-induced T cell immunodeficiency.

Citing Articles

Clonal Evolution of High-Risk Chronic Lymphocytic Leukemia: A Contemporary Perspective.

Kwok M, Wu C Front Oncol. 2022; 11:790004.

PMID: 34976831 PMC: 8716560. DOI: 10.3389/fonc.2021.790004.

Bringing Macrophages to the Frontline against Cancer: Current Immunotherapies Targeting Macrophages.

Reis-Sobreiro M, Teixeira da Mota A, Jardim C, Serre K Cells. 2021; 10(9).

PMID: 34572013 PMC: 8464913. DOI: 10.3390/cells10092364.

Chronic lymphocytic leukemia-like monoclonal B-cell lymphocytosis exhibits an increased inflammatory signature that is reduced in early-stage chronic lymphocytic leukemia.

Blanco G, Puiggros A, Sherry B, Nonell L, Calvo X, Puigdecanet E Exp Hematol. 2021; 95:68-80.

PMID: 33421548 PMC: 9135325. DOI: 10.1016/j.exphem.2020.12.007.

iNOS Interacts with Autophagy Receptor p62 and is Degraded by Autophagy in Macrophages.

Wang J, Wu M, Su H, Lu J, Chen X, Tan J Cells. 2019; 8(10).

PMID: 31618870 PMC: 6829587. DOI: 10.3390/cells8101255.

Investigation of factors affecting the efficacy of 3C23K, a human monoclonal antibody targeting MISIIR.

Gill S, Zhang Q, Keeney G, Cliby W, Weroha S Oncotarget. 2017; 8(49):85214-85223.

PMID: 29156714 PMC: 5689604. DOI: 10.18632/oncotarget.19620.

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