Abstract

Identification of the different elements intervening at the tumor microenvironment seems key to explain clinical evolution in several tumor types. In this study, a set of immune biomarkers (myeloid derived suppressor cells, regulatory T cells, and OX40 + and PD-1 + T lymphocytes counts) in peripheral blood of patients diagnosed with advanced breast cancer were analyzed along of first line antineoplastic therapy. Subsequently, a comparison between groups with clinical benefit versus progression of disease and with a healthy women cohort was executed. Results reflected that patients showed higher basal levels of myeloid derived suppressor cells (35.43, IR = 180.73 vs 17.53, IR = 16.96 cells/μl; p = 0.001) and regulatory T cells (32.05, IR = 29.84 vs 22.61, IR = 13.57 cells/μl; p = 0.001) in comparison with healthy women. Furthermore, an increase in the number of activated T lymphocytes (expressing OX40), a decrease of immune inhibitory cells (MDSCs and Tregs) and inhibited T lymphocytes (expressing PD-1) were observed along the treatment in patients with clinical benefit (p ≤ 0.001). The opposite trend was observed in the case of disease progression. These findings suggest that some critical immune elements can be easily detected and measured in peripheral blood, which open a new opportunity for translational research, as they seem to be correlated with clinical evolution, at least in ABC.

Highlights

  • Identification of the different elements intervening at the tumor microenvironment seems key to explain clinical evolution in several tumor types

  • Patients received 1st line treatment for ABC following local protocols based on International Guidelines and according to the tumor subtype based on the expression of RE/RP and HER2. 61% were treated with cyclin-dependent kinase 4/6 inhibitors plus hormonotherapy, 18% with hormonotherapy alone, 16% received chemotherapy, 6% were treated with anti-her[2] monoclonal antibodies and 2% with chemoimmunotherapy

  • By 13 February 2020, the following basal measurements from peripheral blood were taken: CD8+T and CD4+T lymphocytes with expression of OX40, CD8+T and CD4+T lymphocytes with expression of progression of disease (PD)-1, Tregs and myeloid derived suppressor cells (MDSCs) levels

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Summary

Introduction

Identification of the different elements intervening at the tumor microenvironment seems key to explain clinical evolution in several tumor types. Density and function of some immune cell populations seem related to the response to treatment and prognosis of ­cancer[4,5,6,7] and, interestingly, they can be detected and measured not just in TME but even in peripheral blood, what renders many advantages over tissue b­ iopsies[8] At this point, myeloid derived suppressor cells (MDSCs) and different lymphocyte subpopulations, such as regulatory T cells (Tregs)[4], activated CD4 + and CD8 + T lymphocytes (expressing OX40) or inhibited T lymphocytes (expressing PD-1)[9,10], and other subset of cells can be measured in peripheral blood of patients with ­BC2,5,11–13. MDSCs are generally defined by CD45+CD3-CD19-CD20-CD56-CD16-HLADR-CD33+CD11b+expression through flow cytometry, being CD14 + and CD15 + subsets assigned as monocytic and granulocytic MDSCs, r­ espectively[19]

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