From the “missing self” hypothesis to adaptive NK cells: Insights of NK cell-mediated effector functions in immune surveillance

Abstract

The original discovery of NK cells approximately 40 yr ago was based on their unique capability to kill tumor cells without prior sensitization or priming, a process named natural cytotoxicity. Since then, several studies have documented that NK cells can kill hematopoietic and nonhematopoietic cancer cells. NK cells also recognize and kill cells that have undergone viral infections. Besides natural cytotoxicity, NK cells are also major effectors of antibody‐dependent cell cytotoxicity (ADCC). Therefore, NK cells are well “armed” to recognize and mount immune responses against “insults” that result from cell transformation and viral infections. Because of these attributes, an essential role of NK cells in tumor surveillance was noted. Indeed, several studies have shown a correlation between impaired NK cell cytotoxicity and a higher risk of developing cancer. This evidence led to the idea that cancer initiation and progress is intimately related to an abnormal or misdirected immune response. Whereas all these ideas remain current, it is also true that NK cells represent a heterogeneous population with different abilities to secrete cytokines and to mediate cytotoxic functions. In addition, recent data has shown that NK cells are prone to suffer epigenetic modifications resulting in the acquisition of previously unrecognized attributes such as memory and long‐term survival. Such NK cells, referred as “adaptive” or “memory‐like,” also display effector functions that are not necessarily equal to those observed in conventional NK cells. Given the new evidence available, it is essential to discuss the conceptual reasoning and misconceptions regarding the role of NK cells in immune surveillance and immunotherapy.

Functional characterization of NK cells in Mexican pediatric patients with acute lymphoblastic leukemia: Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

“…Among immune cells, NK cells play an important role in recognizing and killing leukemia cells [22,38]. In consequence, NK cell-based immunotherapies have proven to be successful in the treatment of high-risk leukemia [38,43]. However, it is also noticed that not all leukemias, either myeloid or lymphoid, are equally susceptible to these cellbased therapy regimens.…”

Non-Coated Rituximab Induces Highly Cytotoxic Natural Killer Cells From Peripheral Blood Mononuclear Cells via Autologous B Cells

“…NK cells are important innate immune cells which are closely related to tumorigenesis and metastasis ( 2 ). In vitro and in vivo studies have demonstrated that NK cells can exert a powerful antitumor function without pro-stimulation.…”

“…Natural killer (NK) cells are important innate immune cells that play essential roles in tumor surveillance ( 1 , 2 ). The function and number of NK cells in patients with cancer are usually diminished compared to healthy individuals ( 3 , 4 ).…”

Natural Killer Cells in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis - A Review of the Literature

“…The exact role for NK cells in autoimmunity is still controversial and data support both pathogenic and protective functions. On one hand, NK cells could directly participate in destroying host tissue, produce high levels of pro-inflammatory cytokines and kill T regulatory cells that normally prevent autoimmunity ( 30 – 32 ). On the other hand, NK cells do not only have cytotoxic functions, but can also secrete inhibitory cytokines, such as IL-10 and TGFβ, thus leading to a down regulation of the immune system and can block autoreactive CD8 + T cells ( 33 ).…”