Effectiveness limitation reasons include limited transferred NK cell persistence in the body, restricted migration and penetration ability into tumor tissues compared to other immune system cells, the evolution of NK cell escape mechanisms in tumor cells, and finally, NK cells inhibition by TME component amongst Treg, myeloid-derived suppressor cells (MDSC) that cause NK cells function inhibition and transforming growth factor-β (TGF-β), adenosine, prostaglandin E2 (PGE2) and indoleamine 2,3-dioxygenase (IDO) which have been associated to NK cell dysfunction [80]. Here, IDO2 is linked to neoplasm.