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PLoS One. 2012;7(4):e32614. doi: 10.1371/journal.pone.0032614. Epub 2012 Apr 2.

Monitoring of regulatory T cell frequencies and expression of CTLA-4 on T cells, before and after DC vaccination, can predict survival in GBM patients.

Author information

1
Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, California, United States of America.

Erratum in

  • PLoS One. 2012;7(4): doi/10.1371/annotation/921cda8a-d169-49b8-9dfc-5ee32271b729.
  • PLoS One. 2012;7(4): doi/10.1371/annotation/641c3e73-ee2c-4873-8896-1b3a2edc557b.

Abstract

PURPOSE:

Dendritic cell (DC) vaccines have recently emerged as an innovative therapeutic option for glioblastoma patients. To identify novel surrogates of anti-tumor immune responsiveness, we studied the dynamic expression of activation and inhibitory markers on peripheral blood lymphocyte (PBL) subsets in glioblastoma patients treated with DC vaccination at UCLA.

EXPERIMENTAL DESIGN:

Pre-treatment and post-treatment PBL from 24 patients enrolled in two Phase I clinical trials of dendritic cell immunotherapy were stained and analyzed using flow cytometry. A univariate Cox proportional hazards model was utilized to investigate the association between continuous immune monitoring variables and survival. Finally, the immune monitoring variables were dichotomized and a recursive partitioning survival tree was built to obtain cut-off values predictive of survival.

RESULTS:

The change in regulatory T cell (CD3(+)CD4(+)CD25(+)CD127(low)) frequency in PBL was significantly associated with survival (p = 0.0228; hazard ratio = 3.623) after DC vaccination. Furthermore, the dynamic expression of the negative co-stimulatory molecule, CTLA-4, was also significantly associated with survival on CD3(+)CD4(+) T cells (p = 0.0191; hazard ratio = 2.840) and CD3(+)CD8(+) T cells (p = 0.0273; hazard ratio = 2.690), while that of activation markers (CD25, CD69) was not. Finally, a recursive partitioning tree algorithm was utilized to dichotomize the post/pre fold change immune monitoring variables. The resultant cut-off values from these immune monitoring variables could effectively segregate these patients into groups with significantly different overall survival curves.

CONCLUSIONS:

Our results suggest that monitoring the change in regulatory T cell frequencies and dynamic expression of the negative co-stimulatory molecules on peripheral blood T cells, before and after DC vaccination, may predict survival. The cut-off point generated from these data can be utilized in future prospective immunotherapy trials to further evaluate its predictive validity.

PMID:
22485134
PMCID:
PMC3317661
DOI:
10.1371/journal.pone.0032614
[Indexed for MEDLINE]
Free PMC Article
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