Oncotarget

Research Papers:

Impact of lenalidomide maintenance on the immune environment of multiple myeloma patients with low tumor burden after autologous stem cell transplantation

Karel Fostier _, Jo Caers, Nathalie Meuleman, Katrijn Broos, Jurgen Corthals, Kris Thielemans, Rik Schots and Brenda De Keersmaecker

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Oncotarget. 2018; 9:20476-20489. https://doi.org/10.18632/oncotarget.24944

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Abstract

Karel Fostier1, Jo Caers2, Nathalie Meuleman3, Katrijn Broos4, Jurgen Corthals4, Kris Thielemans4, Rik Schots1 and Brenda De Keersmaecker4

1Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Department of Hematology, Brussels, Belgium

2Centre Hospitalier Universitaire (CHU) de Liège, Department of Hematology, Liège, Belgium

3Institut Jules Bordet, Department of Hematology, Brussels, Belgium

4Vrije Universiteit Brussel (VUB), Laboratory of Molecular and Cellular Therapy, Brussels, Belgium

Correspondence to:

Karel Fostier, email: Karel.Fostier@uzbrussel.be

Keywords: lenalidomide; immunomodulation

Received: July 26, 2017     Accepted: February 27, 2018     Published: April 17, 2018

ABSTRACT

Lenalidomide is a potent anti-myeloma drug with immunomodulatory properties. It is increasingly used in a low-dose maintenance setting to prolong remission duration after standard treatment. Data on the in vivo effects of lenalidomide are scarce and sometimes different from the well-described in vitro effects. We therefore evaluated the numerical, phenotypical and functional impact of lenalidomide maintenance on several immune cell types in a cohort of seventeen homogeneously treated myeloma patients achieving a low residual myeloma burden after a bortezomib based-induction followed by autologous stem cell transplantation. Lenalidomide maintenance: 1) increased the fraction of naïve CD8+ T cells and several memory T-cell subsets, 2) reduced the numbers of terminal effector CD8+ T cells, 3) resulted in a higher expression of co-stimulatory molecules on resting T cells and of the inhibitory checkpoint molecules LAG-3 on CD4+ T cells and TIM-3 on CD4+ and CD8+ T cells, 4) reduced the number of TIGIT+ CD8+ T cells, 5) increased the number of regulatory T cells with a phenotype associated with strong suppressive capacity. Purified CD8+ T cells showed increased and more polyfunctional recall viral responses. However, PBMC responses were not enhanced during lenalidomide maintenance and CD4+ T-cell responses specific for the myeloma-associated antigen MAGE-C1 even tended to become lower. We conclude that lenalidomide maintenance after autologous stem cell transplantation has complex pleotropic effects on the immune environment. Immune interventions such as anti-myeloma vaccination should include measures to tackle an expanded inhibitory Treg compartment.


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