Cord Blood-Derived Natural Killer Cell Exploitation in Immunotherapy Protocols: More Than a Promise?

Abstract

Simple SummaryNK cell anti-tumor activity against hematological malignancies is well-established and many studies support their role in the control of solid tumor growth and metastasis generation. However, tumor microenvironment may affect NK cell function. Ongoing studies are aimed to design novel immunotherapeutic protocols to combine NK cell-based immunotherapy with other therapeutic strategies to improve the anti-tumor NK cell response. In this context, UCB is one of the main sources of both mature NK cells and of CD34+ HSPC that can generate NK cells, both in-vivo and in-vitro. UCB-derived NK cells represent a valuable tool to perform in-vitro and preclinical analyses and are already used in several clinical settings, particularly against hematological malignancies. The present review describes the characteristics of different types of UCB-derived NK cells and the in-vitro models to expand them, both for research and clinical purposes in the context of cancer immunotherapy.In the last 20 years, Natural Killer (NK) cell-based immunotherapy has become a promising approach to target various types of cancer. Indeed, NK cells play a pivotal role in the first-line defense against tumors through major histocompatibility complex-independent immunosurveillance. Their role in the control of leukemia relapse has been clearly established and, moreover, the presence of NK cells in the tumor microenvironment (TME) generally correlates with good prognosis. However, it has also been observed that, often, NK cells poorly infiltrate the tumor tissue, and, in TME, their functions may be compromised by immunosuppressive factors that contribute to the failure of anti-cancer immune response. Currently, studies are focused on the design of effective strategies to expand NK cells and enhance their cytotoxic activity, exploiting different cell sources, such as peripheral blood (PB), umbilical cord blood (UCB) and NK cell lines. Among them, UCB represents an important source of mature NK cells and CD34+ Hematopoietic Stem and Progenitor Cells (HSPCs), as precursors of NK cells. In this review, we summarize the UCB-derived NK cell activity in the tumor context, review the different in-vitro models to expand NK cells from UCB, and discuss the importance of their exploitation in anti-tumor immunotherapy protocols.