However, cancer-initiating cells (CICs) escaping immune recognition, elevated Treg, M2 macrophage and MDSC counts in the tumor microenvironment, immunosuppressive factors (i.e., IL-1, TGF-β, IL-10, arginase I), apoptosis-inducers (i.e., CD95, CD70), tumor hypoxia and immune checkpoint inhibitors are major challenges also for NK cell-based immunotherapies (Nduom et al., 2015; Maccalli et al., 2017; Multhoff and Vaupel, 2020). This evidence concerns the gene IL10 and cancer.