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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 6/2016

01-06-2016 | Original Article

Disease progression in recurrent glioblastoma patients treated with the VEGFR inhibitor axitinib is associated with increased regulatory T cell numbers and T cell exhaustion

Authors: Stephanie Du Four, Sarah K. Maenhout, Daphné Benteyn, Brenda De Keersmaecker, Johnny Duerinck, Kris Thielemans, Bart Neyns, Joeri L. Aerts

Published in: Cancer Immunology, Immunotherapy | Issue 6/2016

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Abstract

Background

Recurrent glioblastoma is associated with a poor overall survival. Antiangiogenic therapy results in a high tumor response rate but has limited impact on survival. Immunotherapy has emerged as an efficient treatment modality for some cancers, and preclinical evidence indicates that anti-VEGF(R) therapy can counterbalance the immunosuppressive tumor microenvironment.

Methods

We collected peripheral blood mononuclear cells (PBMC) of patients with recurrent glioblastoma treated in a randomized phase II clinical trial comparing the effect of axitinib with axitinib plus lomustine and analyzed the immunophenotype of PBMC, the production of cytokines and expression of inhibitory molecules by circulating T cells.

Results

PBMC of 18 patients were collected at baseline and at 6 weeks after initiation of study treatment. Axitinib increased the number of naïve CD8+ T cells and central memory CD4+ and CD8+ T cells and reduced the TIM3 expression on CD4+ and CD8+ T cells. Patients diagnosed with progressive disease on axitinib had a significantly increased number of regulatory T cells and an increased level of PD-1 expression on CD4+ and CD8+ T cells. In addition, reduced numbers of cytokine-producing T cells were found in progressive patients as compared to patients responding to treatment.

Conclusion

Our results suggest that axitinib treatment in patients with recurrent glioblastoma has a favorable impact on immune function. At the time of acquired resistance to axitinib, we documented further enhancement of a preexisting immunosuppression. Further investigations on the role of axitinib as potential combination partner with immunotherapy are necessary.
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Metadata
Title
Disease progression in recurrent glioblastoma patients treated with the VEGFR inhibitor axitinib is associated with increased regulatory T cell numbers and T cell exhaustion
Authors
Stephanie Du Four
Sarah K. Maenhout
Daphné Benteyn
Brenda De Keersmaecker
Johnny Duerinck
Kris Thielemans
Bart Neyns
Joeri L. Aerts
Publication date
01-06-2016
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 6/2016
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-016-1836-3

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