Abstract
Tumors affect the immune system, locally and systemically. The frequencies of specific circulating immune cell populations correlate with disease progression as well as prognosis of the patients. Although largely neglected, conventional antitumoral therapies often possess immunomodulatory properties and affect the levels of specific immune cell populations. Most information, however, derive from animal or in vitro studies. As this could impact prognosis as well as response to therapy, further studies of the effects of treatment on circulating immune cells in patients are warranted. In this pilot study, we evaluated a wide panel of circulating immune cells over time (up to six months) in ten patients with metastatic breast cancer receiving standard antitumoral regimens. Overall, endocrine therapy tends to enrich for natural killer (NK) and natural killer T (NKT) cells in the circulation, whereas both chemotherapy and endocrine therapy reduce the levels of circulating monocytic myeloid-derived suppressor cells (Mo-MDSCs). This indicates that the systemic immunosuppressive profile observed in patients tends to revert over the course of systemic therapy and holds promise for future combination treatment with standard antitumoral agents and immunotherapy.
Highlights
Breast cancer is the most common cancer in women worldwide, with more than 2.4 million new cases annually[1]
New targeted therapies have been introduced for subgroups of metastatic breast cancer (MBC) patients, such as cycline-dependent-kinase inhibitors (CDK-I) in combination with endocrine therapy in ER positive disease[8,9] and currently, check-point inhibitors are being introduced in clinical practice for TNBC10
One patient was diagnosed with early progression at first evaluation whereas the mean progression-free survival (PFS) was 23 months
Summary
Breast cancer is the most common cancer in women worldwide, with more than 2.4 million new cases annually[1]. Regulatory T cells (Tregs), Th2-skewed T helper cells (Th), anti-inflammatory neutrophils or macrophages (N2 neutrophils and M2 macrophages) and myeloid-derived suppressor cells (MDSCs) are involved in immunosuppression, tissue remodeling and angiogenesis, and are regarded pro-tumorigenic[12,13]. Today it is a well-documented fact that tumors actively modulate the immune system towards a more tumor-permissive phenotype, locally as well as systemically. Decreased levels of circulating lymphocytes (especially CD8+ CTLs) and myeloid dendritic cells (mDCs) or increased levels of monocytes, NK cells, Tregs and MDSCs correlate with stage and/or disease progression[17,18,19,20,21,22,23]
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