Circulating immune biomarkers in peripheral blood correlate with clinical outcomes in advanced breast cancer

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.

Pembrolizumab Plus Gemcitabine in the Subset of Triple-Negative Advanced Breast Cancer Patients in the GEICAM/2015-04 (PANGEA-Breast) Study

“…Therefore, it can be inferred that tumors induce an immunosuppressive status that can be easily measured using blood samples in the patients. These findings in BC were previously suggested by our group and other researchers [15][16][17][18]. In an attempt to deplete MDSCs levels and improve clinical outcomes by boosting the immune response, gemcitabine was chosen as a partner of pembrolizumab in this work [7].…”

Leveraging the Dynamic Immune Environment Triad in Patients with Breast Cancer: Tumour, Lymph Node, and Peripheral Blood

“…A high neutrophil to lymphocyte ratio is associated with a worse prognosis in multiple breast cancer subtypes [ 23 , 24 ], and a high lymphocyte to monocyte ratio is predictive of an improved response to treatment [ 23 ]. High circulating lymphocyte counts are consistently associated with better outcomes [ 25 ]. Intriguingly, increased TIL levels (>50%) at the primary tumour do not correlate with increased absolute circulating lymphocyte counts in breast cancer patients and are negatively associated with absolute circulating neutrophil counts [ 42 ].…”

Tumor Immune Microenvironment in Lymphoma: Focus on Epigenetics

“…Myeloid derived suppressor cells (MDSCs): MDSCs, originated from immature myeloid cells, are a group of heterogeneous cells characterized by suppressing immune responses [90]. Currently, MDSCs are generally defined by CD45+ CD3− CD19− CD20− CD56− CD16− HLADR− CD33+ CD11b+ through flow cytometry [91].…”

“…Currently, MDSCs are generally defined by CD45+ CD3− CD19− CD20− CD56− CD16− HLADR− CD33+ CD11b+ through flow cytometry [91]. Besides, there are two different subpopulations of MDSCs that can either express CD14 or CD15: monocytic MDSCs (M-MDSCs), which express CD14 and may differentiate into monocytes (such as macrophages and dendritic cells), and granulocytic MDSCs (G-MDSCs), which express CD15 and may differentiate into granulocytes (polymorphonuclear leukocytes) [90][91][92]. MDSCs mainly inhibit T cell immune responses by using different mechanisms, such as reactive oxygen species or nitrogen oxide production [93] and Tregs induction, which contributes to tumor dissemination [94].…”