Limits...
NK cells sense tumors, course of disease and treatments: Consequences for NK-based therapies.

Fregni G, Perier A, Avril MF, Caignard A - Oncoimmunology (2012)

Bottom Line: The recent findings on NK activation indicate that these cells are important antitumor effectors.However, tumor-infiltrating NK cells are yet poorly characterized.We here summarize our results and the recent studies of the literature on tumor-infiltrating NK cells, and discuss the impact of these novel insights into NK cell responses against tumors for the design of NK cell-based therapies.

View Article: PubMed Central - PubMed

Affiliation: Institut Cochin-INSERM U06; CNRS UMR 804; Université Paris Descartes; Paris, France.

ABSTRACT
The recent findings on NK activation indicate that these cells are important antitumor effectors. NK cells participate in the graft-vs.-leukemia effect to control the relapse in leukemic patients transplanted with allogeneic hematopoietic stem cells. In various tumors, correlation between NK cell infiltrates and prognosis were reported. However, tumor-infiltrating NK cells are yet poorly characterized. We here summarize our results and the recent studies of the literature on tumor-infiltrating NK cells, and discuss the impact of these novel insights into NK cell responses against tumors for the design of NK cell-based therapies.

No MeSH data available.


Related in: MedlinePlus

Figure 1. Regulation of NK cell activation. (A) Main NK receptors (lower line) and respective ligands on target cells (upper line) implicated in NK cell triggering and inhibition. (B) Functions of NK cells (cytotoxicity and cytokine secretion) depend on a balance between opposing signals derived from activating and inhibitory receptors. The presence and density of ligands dictate whether the target cell will be susceptible (immune surveillance) or not (self tolerance) to NK cell lysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3376977&req=5

Figure 1: Figure 1. Regulation of NK cell activation. (A) Main NK receptors (lower line) and respective ligands on target cells (upper line) implicated in NK cell triggering and inhibition. (B) Functions of NK cells (cytotoxicity and cytokine secretion) depend on a balance between opposing signals derived from activating and inhibitory receptors. The presence and density of ligands dictate whether the target cell will be susceptible (immune surveillance) or not (self tolerance) to NK cell lysis.

Mentions: Natural Killer cell activation depends on the intricate balance between activating and inhibitory signals derived from receptors. Most inhibitory receptors (KIR, NKG2A, LIR) are specific for different HLA-I molecules. In normal conditions, the low engagement of activating receptors counterbalanced by high inhibitory signals triggered by HLA-I molecules on normal cells avoids self reactivity of NK cells (Fig. 1). In the context of tumor, NK cell activation relies on the expression of NK ligands by target cells. To be “seen” by NK cells, cancer cells have to express ligands for activating receptors, while the low expression of HLA-I molecules attenuates the triggering of inhibitory receptors. Cancer cells can also secrete immuno-modulating molecules inducing immune cell anergy. Thus, tumor-related parameters strongly control NK cell activation and any factor that modifies the expression of NK ligands on tumor cells may thus affect the activation of NK cells.


NK cells sense tumors, course of disease and treatments: Consequences for NK-based therapies.

Fregni G, Perier A, Avril MF, Caignard A - Oncoimmunology (2012)

Figure 1. Regulation of NK cell activation. (A) Main NK receptors (lower line) and respective ligands on target cells (upper line) implicated in NK cell triggering and inhibition. (B) Functions of NK cells (cytotoxicity and cytokine secretion) depend on a balance between opposing signals derived from activating and inhibitory receptors. The presence and density of ligands dictate whether the target cell will be susceptible (immune surveillance) or not (self tolerance) to NK cell lysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376977&req=5

Figure 1: Figure 1. Regulation of NK cell activation. (A) Main NK receptors (lower line) and respective ligands on target cells (upper line) implicated in NK cell triggering and inhibition. (B) Functions of NK cells (cytotoxicity and cytokine secretion) depend on a balance between opposing signals derived from activating and inhibitory receptors. The presence and density of ligands dictate whether the target cell will be susceptible (immune surveillance) or not (self tolerance) to NK cell lysis.
Mentions: Natural Killer cell activation depends on the intricate balance between activating and inhibitory signals derived from receptors. Most inhibitory receptors (KIR, NKG2A, LIR) are specific for different HLA-I molecules. In normal conditions, the low engagement of activating receptors counterbalanced by high inhibitory signals triggered by HLA-I molecules on normal cells avoids self reactivity of NK cells (Fig. 1). In the context of tumor, NK cell activation relies on the expression of NK ligands by target cells. To be “seen” by NK cells, cancer cells have to express ligands for activating receptors, while the low expression of HLA-I molecules attenuates the triggering of inhibitory receptors. Cancer cells can also secrete immuno-modulating molecules inducing immune cell anergy. Thus, tumor-related parameters strongly control NK cell activation and any factor that modifies the expression of NK ligands on tumor cells may thus affect the activation of NK cells.

Bottom Line: The recent findings on NK activation indicate that these cells are important antitumor effectors.However, tumor-infiltrating NK cells are yet poorly characterized.We here summarize our results and the recent studies of the literature on tumor-infiltrating NK cells, and discuss the impact of these novel insights into NK cell responses against tumors for the design of NK cell-based therapies.

View Article: PubMed Central - PubMed

Affiliation: Institut Cochin-INSERM U06; CNRS UMR 804; Université Paris Descartes; Paris, France.

ABSTRACT
The recent findings on NK activation indicate that these cells are important antitumor effectors. NK cells participate in the graft-vs.-leukemia effect to control the relapse in leukemic patients transplanted with allogeneic hematopoietic stem cells. In various tumors, correlation between NK cell infiltrates and prognosis were reported. However, tumor-infiltrating NK cells are yet poorly characterized. We here summarize our results and the recent studies of the literature on tumor-infiltrating NK cells, and discuss the impact of these novel insights into NK cell responses against tumors for the design of NK cell-based therapies.

No MeSH data available.


Related in: MedlinePlus