Polymorphonuclear Myeloid-Derived Suppressor Cells Are Abundant in Peripheral Blood of Cancer Patients and Suppress Natural Killer Cell Anti-Tumor Activity

Abstract

Tumor microenvironment (TME) includes a wide variety of cell types and soluble factors capable of suppressing immune-responses. While the role of NK cells in TME has been analyzed, limited information is available on the presence and the effect of polymorphonuclear (PMN) myeloid-derived suppressor cells, (MDSC). Among the immunomodulatory cells present in TME, MDSC are potentially efficient in counteracting the anti-tumor activity of several effector cells. We show that PMN-MDSC are present in high numbers in the PB of patients with primary or metastatic lung tumor. Their frequency correlated with the overall survival of patients. In addition, it inversely correlated with low frequencies of NK cells both in the PB and in tumor lesions. Moreover, such NK cells displayed an impaired anti-tumor activity, even those isolated from PB. The compromised function of NK cells was consequent to their interaction with PMN-MDSC. Indeed, we show that the expression of major activating NK receptors, the NK cytolytic activity and the cytokine production were inhibited upon co-culture with PMN-MDSC through both cell-to-cell contact and soluble factors. In this context, we show that exosomes derived from PMN-MDSC are responsible of a significant immunosuppressive effect on NK cell-mediated anti-tumor activity. Our data may provide a novel useful tool to implement the tumor immunoscore. Indeed, the detection of PMN-MDSC in the PB may be of prognostic value, providing clues on the presence and extension of both adult and pediatric tumors and information on the efficacy not only of immune response but also of immunotherapy and, possibly, on the clinical outcome.

Exosomes and cancer immunotherapy: A review of recent cancer research

“…have shown that exosomes derived from Tumor-associated macrophages up-regulate miR-192-5p to promote endometrial cancer cells apoptosis and effectively suppress the progression of endometrial cancer ( 60 ). Exosomes secreted by polymorphonuclear (PMN) myeloid-derived suppressor cells (MDSCs), which are immunomodulatory cells present in the TIME, significantly inhibit NK cell-mediated anticancer activity, suggesting that the detection of PMN-MDSC content may have prognostic value ( 61 ). miR-326 in M1 macrophage exosomes promotes apoptosis of liver cancer cells and inhibits cancer proliferation and migration by downregulating the expression of NF-κB in liver cancer ( 62 ).…”

Managing the TME to improve the efficacy of cancer therapy

“…Unfavorable responses can also be predicted, especially when the presence of other types of immune cells (e.g. MDSCs) are detected ( 25 ). Notoriously, in a number of specific cancers, non-malignant cells can far outnumber the malignant ones.…”

Circulating tumor cell-blood cell crosstalk: Biology and clinical relevance

“…Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immune cells originating from the bone marrow myeloid stem cell lineage, with a strong immunosuppressive function. MDSCs interact with other immune cells, including NK cells and T lymphocytes, to regulate their function, although their mechanisms of action have not been elucidated yet (Tumino et al, 2022). In cancer patients, the amount of MDSCs found in circulation are highly increased and it has been associated with an increased number of CTCs (Elbasateeny et al, 2022;Papadaki et al, 2021).…”