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

• Published in: Cancer Immunology, Immunotherapy Immunotherapy, 2013-06, Vol.62 (6), p.1123-1130
• Main Authors: Song, Guohong, Wang, Xiaoli, Jia, Jun, Yuan, Yanhua, Wan, Fengling, Zhou, Xinna, Yang, Huabing, Ren, Jun, Gu, Jiezhun, Lyerly, Herbert Kim
• Format: Article
• Language: English
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-013-1424-8

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- gamma , and transforming growth factor- beta 1 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 super(+)CD28 super(-) and CD4 super(+)CD25 super(+) were elevated in MBC patients compared to the control cohort (P < 0.05). In contrast, CD3 super(+) and CD8 super(+)CD28 super(+)cell s 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 super(+)CD28 super(-) and CD4 super(+)CD25 super(+) cells showed increased levels of IL-6, and only patients with elevated CD8 super(+)CD28 super(-) had decreased interferon- gamma . Univariate analysis indicated increased CD3 super(+)CD4 super(+) or CD8 super(+)CD28 super(+)corr elated with prolonged progression-free survival (PFS), while elevated CD8 super(+)CD28 super(-)associated with shorten PFS. The percent of CD8 super(+)CD28 super(-) T lymphocytes is an independent predictor for PFS through multivariate analysis. Conclusions: This study suggests that progressive elevated levels of CD8 super(+)CD28 super(-) suppressor T lymphocytes represent a novel independent predictor of PFS during post-chemotherapy follow-up.