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01-06-2013 | Original Article

Elevated level of peripheral CD8⁺CD28⁻ T lymphocytes are an independent predictor of progression-free survival in patients with metastatic breast cancer during the course of chemotherapy

Authors: Guohong Song, Xiaoli Wang, Jun Jia, Yanhua Yuan, Fengling Wan, Xinna Zhou, Huabing Yang, Jun Ren, Jiezhun Gu, Herbert Kim Lyerly

Published in: Cancer Immunology, Immunotherapy | Issue 6/2013

Abstract

Purpose

Suppression of cellular immunity resulting from tumorigenesis and/or therapy might promote cancer cells’ growth, progression and invasion. Here, we explored whether T lymphocyte subtypes from peripheral blood of metastatic breast cancer (MBC) female patients could be used as alternative surrogate markers for cancer progress. Additionally, plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IFN-γ, and transforming growth factor-β1 were quantitated from MBC and healthy volunteers.

Experimental design

This study included 89 female MBC patients during the post-salvage chemotherapy follow-up and 50 age- and sex-matched healthy volunteers as control. The percentages of T lymphocyte subpopulations from peripheral blood and plasma levels of cytokines were measured.

Results

Both CD8⁺CD28⁻ and CD4⁺CD25⁺ were elevated in MBC patients compared to the control cohort (P < 0.05). In contrast, CD3⁺ and CD8⁺CD28⁺cells were significantly lower in MBC patients (P < 0.0001, P = 0.045, respectively). MBC patients had elevated levels of immunosuppressive cytokines IL-6 and IL-10. Patients with elevated CD8⁺CD28⁻ and CD4⁺CD25⁺ cells showed increased levels of IL-6, and only patients with elevated CD8⁺CD28⁻ had decreased interferon-γ. Univariate analysis indicated increased CD3⁺CD4⁺ or CD8⁺CD28⁺correlated with prolonged progression-free survival (PFS), while elevated CD8⁺CD28⁻associated with shorten PFS. The percent of CD8⁺CD28⁻ T lymphocytes is an independent predictor for PFS through multivariate analysis.

Conclusions

This study suggests that progressive elevated levels of CD8⁺CD28⁻ suppressor T lymphocytes represent a novel independent predictor of PFS during post-chemotherapy follow-up.

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Title: Elevated level of peripheral CD8+CD28− T lymphocytes are an independent predictor of progression-free survival in patients with metastatic breast cancer during the course of chemotherapy
Authors: Guohong Song
Xiaoli Wang
Jun Jia
Yanhua Yuan
Fengling Wan
Xinna Zhou
Huabing Yang
Jun Ren
Jiezhun Gu
Herbert Kim Lyerly
Publication date: 01-06-2013
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 6/2013
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-013-1424-8

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