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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Acknowledgments
The authors thank Dr. Wei Sun for excellent technical assistance in flow cytometric analysis, Amy Hobeika Ph.D. from Duke university medical center, Durham, NC, USA for assistance with language editing. Authors received financial support from Natural Science Foundation of China (No.81172534) and Komen-Duke Project in China (3833989) from Susan G. Komen for the Cure Foundation.
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Song, G., Wang, X., Jia, J. et al. 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. Cancer Immunol Immunother 62, 1123–1130 (2013). https://doi.org/10.1007/s00262-013-1424-8
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DOI: https://doi.org/10.1007/s00262-013-1424-8