Abstract
Individuals lacking natural killer (NK) cells have persistent viral infections and as a consequence die prematurely. In addition, mice with decreased NK cell function are more susceptible to carcinogen-induced cancers. Current evidence strongly suggests that downregulation of MHC by certain tumors and virally-infected cells results in NK cell attack due to the inability to trigger inhibitory Ly49, KIR, and NKG2A/CD94 class Ia and Ib MHC receptors. Extreme haplotype diversity is present in both mouse and human chromosomal segments coding for NK cell class Ia MHC receptors resulting in different numbers and types of receptors being expressed in individuals and different inbred mouse strains. Whether the absence or presence of a particular NK cell receptor gene is advantageous or deleterious for an individual with respect to immunity to pathogens and cancer is a question of paramount importance. Recent advances in our understanding of NK cell function are due to the identification of activating NK cell receptors, such as Ly49H and NKG2D, for specific viral and tumor ligands (m157 and Rae1, respectively). In a clinical setting, such MHC class I receptor diversity is advantageous with respect to preventing leukemic relapse in individuals treated for leukemia and receiving bone marrow transplants. Further delineation of NK cell receptors and tumor ligands will help researchers to exploit the innate immune system to better treat such diseases.
| Original language | English |
|---|---|
| Pages (from-to) | 610-616 |
| Number of pages | 7 |
| Journal | Cancer Biology and Therapy |
| Volume | 2 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Nov 2003 |
| Externally published | Yes |
Bibliographical note
Funding Information:NK cells are also important mediators of anti-tumor immunity. This is clearly displayed This work was supported in part byan operat- in transgenic mice with severely decreased levels of NK1.1+CD3- (classical mouse NK cell ing grant from the Canadian Institutes for Health phenotype) cells. Such mice have decreased resistance to B16 experimental lung metastases with Federal funds from the National CancerResearch. This project has also been funded in part and RMA tumor outgrowth.6 Furthermore, protection from the development of carcinogen-Institute, National Institutes of Health, under induced tumors is dependent on NK cells.7 NK cell-mediated tumor rejection also C©ontract No. NO1-CO-12400. A.P.M is a scholar functions to evoke long-term T cell memory. Tumor cells expressing CD70, a ligand for of the Canadian Institutes for Health Research the co-stimulatory NK cell expressed CD27, were rejected more efficiently than CD70- 2003 Landes Bioscientumcoer c.e llNs. Inotetre sftinoglry, sDecoinsdatryr cihballuengtei oof nmice that had rejected CD70+ tumors The content of this publication does not neces- with the CD70- parental tumor line resulted in a tumor-specific T cell rejection response.8
ASJC Scopus Subject Areas
- Molecular Medicine
- Oncology
- Pharmacology
- Cancer Research
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
- Research Support, U.S. Gov't, P.H.S.
- Review
