Myeloid Derived Suppressor Cells Interactions With Natural Killer Cells and Pro-angiogenic Activities: Roles in Tumor Progression

Abstract

Myeloid-derived suppressor cells (MDSCs) contribute to the induction of an immune suppressive/anergic, tumor permissive environment. MDSCs act as immunosuppression orchestrators also by interacting with several components of both innate and adaptive immunity. Natural killer (NK) cells are innate lymphoid cells functioning as primary effector of immunity, against tumors and virus-infected cells. Apart from the previously described anergy and hypo-functionality of NK cells in different tumors, NK cells in cancer patients show pro-angiogenic phenotype and functions, similar to decidual NK cells. We termed the pro-angiogenic NK cells in the tumor microenvironment “tumor infiltrating NK” (TINKs), and peripheral blood NK cells in cancer patients “tumor associated NK” (TANKs). The contribution of MDSCs in regulating NK cell functions in tumor-bearing host, still represent a poorly explored topic, and even less is known on NK cell regulation of MDSCs. Here, we review whether the crosstalk between MDSCs and NK cells can impact on tumor onset, angiogenesis and progression, focusing on key cellular and molecular interactions. We also propose that the similarity of the properties of tumor associated/tumor infiltrating NK and MDSC with those of decidual NK and decidual MDSCs during pregnancy could hint to a possible onco-fetal origin of these pro-angiogenic leukocytes.

Myeloid-derived suppressor cells—new and exciting players in lung cancer

“…The criteria for characterizing the phenotype of MDSCs by flow cytometry are relatively defined, and immunosuppressive function is a functional standard defined for MDSCs. While MDSCs were initially described as merely T cell suppressive, emerging evidence suggests that MDSCs also interact with and modulate the function of other immune cells, particularly macrophages (Mø) [29,30], NK cells [31,32], Treg cells [33], and B cells [34]. Moreover, MDSCs, TAMs, and dendritic cells (DCs) have been reported to interact and cross-promote their immunosuppressive activities in the tumor microenvironment [35].…”

CyTOF analysis identifies unusual immune cells in urine of BCG-treated bladder cancer patients

“…A striking finding from these analyses is the presence in many samples of a population of cells expressing markers of both granulocytes and monocytes, reminiscent of other cell subtypes that have been defined in inflammatory or tumour microenvironments. One hypothesis was that CD14 + CD15 + cells could be MDSC, which derive from a common hematopoietic progenitor cell and can express CD14 and CD15 (Bronte et al, 2016;Bruno et al, 2019;Gabrilovich, 2017). In particular, non-classical CD14 + CD15 + MDSC have been described in lung and colon cancer (Mandruzzato et al, 2009;Vasquez-Dunddel et al, 2013).…”

Targeting Natural Killer Cells for Tumor Immunotherapy

“…MDSCs suppress NK cell cytotoxicity and cytokine secretion via membrane-bound TGF-β on MDSCs in a cell-contact-dependent manner or dependent on NKp30 on NK cells (39,41). Several proinflammatory cytokines have also been reported to contribute to MDSC-mediated NK cell inhibition, resulting in reduced NK cytotoxicity, decreased expression of activating receptor NKGD or NKR, and limited release of IFN-γ (42). These soluble factors include TGF-β, IDO, nitric oxide (NO), and adenosine (38,(43)(44)(45).…”