Depletion of T lymphocytes is correlated with response to temozolomide in melanoma patients

Therapeutic strategies to deplete lymphocytes, especially regulatory T cells, in cancer patients have been proposed to increase the benefits of (immuno)chemotherapy. In this study, we explored the influence of temozolomide (TMZ) on different T-cell populations and addressed if the depletion of CD4+...

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Main Authors:	Iversen, Trine Zeeberg, Brimnes, Marie Klinge, Nikolajsen, Kirsten, Andersen, Rikke Sick, Hadrup, Sine Reker, Andersen, Mads Hald, Bastholt, Lars, Svane, Inge Marie
Format:	Online
Language:	English
Published:	Landes Bioscience 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601183/

id	pubmed-3601183
recordtype	oai_dc
spelling	pubmed-36011832013-03-22 Depletion of T lymphocytes is correlated with response to temozolomide in melanoma patients Iversen, Trine Zeeberg Brimnes, Marie Klinge Nikolajsen, Kirsten Andersen, Rikke Sick Hadrup, Sine Reker Andersen, Mads Hald Bastholt, Lars Svane, Inge Marie Research Paper Therapeutic strategies to deplete lymphocytes, especially regulatory T cells, in cancer patients have been proposed to increase the benefits of (immuno)chemotherapy. In this study, we explored the influence of temozolomide (TMZ) on different T-cell populations and addressed if the depletion of CD4+ T cells would be associated to the clinical benefits of TMZ. Patients were treated with TMZ (150 mg/m2 daily, every two weeks on a four-week schedule) until disease progression. Changes in T-lymphocyte subsets were characterized by flow cytometry. All patients enrolled in this study had histologically verified unresectable stage IV melanoma. Objective responses were induced in 12.5% of the patients, while 42.5% of them obtained short-term disease stabilization. The median progression-free survival (PFS) of this patient cohort was 8.7 mo. Lymphopenia (< 0.7 × 109 cells/L, grade 2) developed in 71% of the patients after 3 treatment cycles (~100 d). The development of grade 2 lymphopenia after the 3rd cycle of therapy positively correlated with clinical outcome (p = 0.01), and was linked, though non-significantly, to prolonged median PFS (303 vs. 200 d). In addition, significant changes in CD8+ T-cell subgroups were observed, notably a shift from naïve T cells toward more differentiated memory T cells. Finally, we demonstrated that specific CD8+ T-cell responses against selected tumor associated antigens (TAAs) were enhanced by the administration of TMZ (p = 0.04), while virus-specific T-cell responses were stable. Thus, immunological monitoring in the course of TMZ treatment might become an important tool for clinical guidance in the future. Landes Bioscience 2013-02-01 /pmc/articles/PMC3601183/ /pubmed/23525955 http://dx.doi.org/10.4161/onci.23288 Text en Copyright © 2013 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Iversen, Trine Zeeberg Brimnes, Marie Klinge Nikolajsen, Kirsten Andersen, Rikke Sick Hadrup, Sine Reker Andersen, Mads Hald Bastholt, Lars Svane, Inge Marie
spellingShingle	Iversen, Trine Zeeberg Brimnes, Marie Klinge Nikolajsen, Kirsten Andersen, Rikke Sick Hadrup, Sine Reker Andersen, Mads Hald Bastholt, Lars Svane, Inge Marie Depletion of T lymphocytes is correlated with response to temozolomide in melanoma patients
author_facet	Iversen, Trine Zeeberg Brimnes, Marie Klinge Nikolajsen, Kirsten Andersen, Rikke Sick Hadrup, Sine Reker Andersen, Mads Hald Bastholt, Lars Svane, Inge Marie
author_sort	Iversen, Trine Zeeberg
title	Depletion of T lymphocytes is correlated with response to temozolomide in melanoma patients
title_short	Depletion of T lymphocytes is correlated with response to temozolomide in melanoma patients
title_full	Depletion of T lymphocytes is correlated with response to temozolomide in melanoma patients
title_fullStr	Depletion of T lymphocytes is correlated with response to temozolomide in melanoma patients
title_full_unstemmed	Depletion of T lymphocytes is correlated with response to temozolomide in melanoma patients
title_sort	depletion of t lymphocytes is correlated with response to temozolomide in melanoma patients
description	Therapeutic strategies to deplete lymphocytes, especially regulatory T cells, in cancer patients have been proposed to increase the benefits of (immuno)chemotherapy. In this study, we explored the influence of temozolomide (TMZ) on different T-cell populations and addressed if the depletion of CD4+ T cells would be associated to the clinical benefits of TMZ. Patients were treated with TMZ (150 mg/m2 daily, every two weeks on a four-week schedule) until disease progression. Changes in T-lymphocyte subsets were characterized by flow cytometry. All patients enrolled in this study had histologically verified unresectable stage IV melanoma. Objective responses were induced in 12.5% of the patients, while 42.5% of them obtained short-term disease stabilization. The median progression-free survival (PFS) of this patient cohort was 8.7 mo. Lymphopenia (< 0.7 × 109 cells/L, grade 2) developed in 71% of the patients after 3 treatment cycles (~100 d). The development of grade 2 lymphopenia after the 3rd cycle of therapy positively correlated with clinical outcome (p = 0.01), and was linked, though non-significantly, to prolonged median PFS (303 vs. 200 d). In addition, significant changes in CD8+ T-cell subgroups were observed, notably a shift from naïve T cells toward more differentiated memory T cells. Finally, we demonstrated that specific CD8+ T-cell responses against selected tumor associated antigens (TAAs) were enhanced by the administration of TMZ (p = 0.04), while virus-specific T-cell responses were stable. Thus, immunological monitoring in the course of TMZ treatment might become an important tool for clinical guidance in the future.
publisher	Landes Bioscience
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601183/
_version_	1611963547539996672

Depletion of T lymphocytes is correlated with response to temozolomide in melanoma patients

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