Beyond Immunosuppression: The Multifaceted Functions of Tumor-Promoting Myeloid Cells in Breast Cancers

Abstract

Breast cancers are commonly associated with an immunosuppressive microenvironment responsible for tumor escape from anti-cancer immunity. Cells of the myeloid lineage account for a major part of this tumor-promoting landscape. These myeloid cells are composed of heterogeneous subsets at different stages of differentiation and have traditionally been described by their cardinal ability to suppress innate and adaptive anticancer immunity. However, evidence has accumulated that, beyond their immunosuppressive properties, breast cancer-induced myeloid cells are also equipped with a broad array of “non-immunological” tumor-promoting functions. They therefore represent major impediments for anticancer therapies, particularly for immune-based interventions. We herein analyze and discuss current literature related to the versatile properties of the different myeloid cell subsets engaged in breast cancer development. We critically assess persisting difficulties and challenges in unequivocally discriminate dedicated subsets, which has so far prevented both the selective targeting of these immunosuppressive cells and their use as potential biomarkers. In this context, we propose the concept of IMCGL, “pro-tumoral immunosuppressive myeloid cells of the granulocytic lineage”, to more accurately reflect the contentious nature and origin of granulocytic cells in the breast tumor microenvironment. Future research prospects related to the role of this myeloid landscape in breast cancer are further considered.

Hormone Receptor Signaling and Breast Cancer Resistance to Anti-Tumor Immunity

“…"HER2-enriched" breast cancers are characterized by an amplification of HER2, and basal-like breast cancers correspond roughly to triple-negative breast cancers, which are HR − /HER2 − [8][9][10][11]. Further characterization of their tumor microenvironment (TME) reveals that these subtypes also differ in the composition of non-malignant elements, which may significantly impact responses to immunotherapies [12]. As such, TNBC patients, whose tumors are considered to be more immunogenic, are more responsive to an immune checkpoint blockade (ICB), such as immune inhibitory receptor PD1 inhibition [13,14].…”

“…Myeloid cells encompass highly heterogeneous subpopulations, play a variety of roles in BC, and are considered the main drivers of tumor progression [12,[102][103][104]. Recent studies have reported that estrogen signaling contributes to the dysregulation of myelopoiesis observed in cancers [100].…”

Myeloid‑derived suppressor cells as targets of emerging therapies and nanotherapies (Review)

“…In BC, MDSC accumulation in the TME and peripheral circulation is notable, driven by the modulation of immunosuppressive mechanisms, predominantly through T-cell activation inhibition ( 17 ), along with the secretion of multiple cytokines and non-immunosuppressive pathways ( 18 ). This collective action promotes tumor growth by enabling tumor angiogenesis, enhancing invasion and metastasis, and modifying the TME to favor tumor progression ( 19 ).…”