NK cell-based immunotherapy for treating cancer: will it be promising?

Abstract

The characterization of natural killer (NK) cells initially occurred in the 1970s and 1980s as a result of efforts by investigators such as Rolf Kiessling and Ronald Heberman. It was observed that a certain population of cells, freshly isolated from normal, unimmunized hosts, could lyse allogeneic tumor cells without sensitization. At the time, these cells were just considered to be a population of non-T, non-B lymphocytes. After the introduction of modern technologies such as monoclonal antibody (mAb) production technology and flow cytometry, the population has been identified as NK cells, phenotypically defined as CD56+ CD3-. Nowadays, it is well known that NK cells have a role as killer cells as well as immunoregulatory cells secreting cytokines and chemokines. Contrary to traditional views, NK cells have recently been shown to require a process called licensing or education to acquire full function by recognition of self-MHC class I during maturation. NK cells are derived from CD34+ hematopoietic progenitor cells and have the morphology of large granular lymphocytes. They can directly kill target cells via the perforin-granzyme pathway, antibody-dependent cellular cytotoxicity (ADCC), and death receptor ligand-induced apoptosis. Such ligands include tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand. Human NK cells can be classified into two subsets; CD56dim (90%) and CD56bright (10%). The CD56dim subset has high cytotoxic activity and expresses a low-affinity receptor for the constant region of immunoglobulin G, FcγRIIIa (CD16), while the CD56bright subset has the capacity to produce abundant cytokines.