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Critical Role of Tumor Microenvironment in Shaping NK Cell Functions: Implication of Hypoxic Stress.

Hasmim M, Messai Y, Ziani L, Thiery J, Bouhris JH, Noman MZ, Chouaib S - Front Immunol (2015)

Bottom Line: Blurring the boundary between innate and adaptive immune system, natural killer (NK) cells, a key component of the innate immunity, are recognized as potent anticancer mediators.Extensive studies have been detailed on how NK cells get activated and recognize cancer cells.This will be followed by a discussion on the role of hypoxic stress in the regulation of NK cell functions.

View Article: PubMed Central - PubMed

Affiliation: INSERM U 1186, Equipe labellisée Ligue Contre le Cancer, Gustave Roussy Campus , Villejuif , France.

ABSTRACT
Blurring the boundary between innate and adaptive immune system, natural killer (NK) cells, a key component of the innate immunity, are recognized as potent anticancer mediators. Extensive studies have been detailed on how NK cells get activated and recognize cancer cells. In contrast, few studies have been focused on how tumor microenvironment-mediated immunosubversion and immunoselection of tumor-resistant variants may impair NK cell function. Accumulating evidences indicate that several cell subsets (macrophages, myeloid-derived suppressive cells, T regulatory cells, dendritic cells, cancer-associated fibroblasts, and tumor cells), their secreted factors, as well as metabolic components (i.e., hypoxia) have immunosuppressive roles in the tumor microenvironment and are able to condition NK cells to become anergic. In this review, we will describe how NK cells react with different stromal cells in the tumor microenvironment. This will be followed by a discussion on the role of hypoxic stress in the regulation of NK cell functions. The aim of this review is to provide a better understanding of how the tumor microenvironment impairs NK cell functions, thereby limiting the use of NK cell-based therapy, and we will attempt to suggest more efficient tools to establish a more favorable tumor microenvironment to boost NK cell cytotoxicity and control tumor progression.

No MeSH data available.


Related in: MedlinePlus

Interactions between NK and stromal cells within the solid tumor microenvironment. Activating and inhibiting interactions of stromal cells with NK cells in the tumor microenvironment.  : secretion; ▬ : membrane-bound; (+): activation; (−): inhibition.
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Figure 1: Interactions between NK and stromal cells within the solid tumor microenvironment. Activating and inhibiting interactions of stromal cells with NK cells in the tumor microenvironment. : secretion; ▬ : membrane-bound; (+): activation; (−): inhibition.

Mentions: Natural killer cells enter solid tumor site by extravasations through tumor vasculature (10). CXCR3 is a major chemokine receptor involved in NK cell migration toward tumor following a gradient of the tumor-derived chemokine (C-X-C motif) ligands CXCL9, 10, and 11 (11, 12). In particular, increased CXCL10 expression in melanoma tumors results in increased infiltration of adoptively transferred CXCR3-positive expanded NK cells, reflecting the role of CXCL10-induced chemoattraction (12). However, infiltrated NK cells often display a suppressed phenotype inside solid tumors. Accumulating evidence indicates that tumor-residing cells as well as a series of microenvironmental factors are endowed with suppressive properties that affect NK cell reactivity and inhibit their functions (Figure 1).


Critical Role of Tumor Microenvironment in Shaping NK Cell Functions: Implication of Hypoxic Stress.

Hasmim M, Messai Y, Ziani L, Thiery J, Bouhris JH, Noman MZ, Chouaib S - Front Immunol (2015)

Interactions between NK and stromal cells within the solid tumor microenvironment. Activating and inhibiting interactions of stromal cells with NK cells in the tumor microenvironment.  : secretion; ▬ : membrane-bound; (+): activation; (−): inhibition.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585210&req=5

Figure 1: Interactions between NK and stromal cells within the solid tumor microenvironment. Activating and inhibiting interactions of stromal cells with NK cells in the tumor microenvironment. : secretion; ▬ : membrane-bound; (+): activation; (−): inhibition.
Mentions: Natural killer cells enter solid tumor site by extravasations through tumor vasculature (10). CXCR3 is a major chemokine receptor involved in NK cell migration toward tumor following a gradient of the tumor-derived chemokine (C-X-C motif) ligands CXCL9, 10, and 11 (11, 12). In particular, increased CXCL10 expression in melanoma tumors results in increased infiltration of adoptively transferred CXCR3-positive expanded NK cells, reflecting the role of CXCL10-induced chemoattraction (12). However, infiltrated NK cells often display a suppressed phenotype inside solid tumors. Accumulating evidence indicates that tumor-residing cells as well as a series of microenvironmental factors are endowed with suppressive properties that affect NK cell reactivity and inhibit their functions (Figure 1).

Bottom Line: Blurring the boundary between innate and adaptive immune system, natural killer (NK) cells, a key component of the innate immunity, are recognized as potent anticancer mediators.Extensive studies have been detailed on how NK cells get activated and recognize cancer cells.This will be followed by a discussion on the role of hypoxic stress in the regulation of NK cell functions.

View Article: PubMed Central - PubMed

Affiliation: INSERM U 1186, Equipe labellisée Ligue Contre le Cancer, Gustave Roussy Campus , Villejuif , France.

ABSTRACT
Blurring the boundary between innate and adaptive immune system, natural killer (NK) cells, a key component of the innate immunity, are recognized as potent anticancer mediators. Extensive studies have been detailed on how NK cells get activated and recognize cancer cells. In contrast, few studies have been focused on how tumor microenvironment-mediated immunosubversion and immunoselection of tumor-resistant variants may impair NK cell function. Accumulating evidences indicate that several cell subsets (macrophages, myeloid-derived suppressive cells, T regulatory cells, dendritic cells, cancer-associated fibroblasts, and tumor cells), their secreted factors, as well as metabolic components (i.e., hypoxia) have immunosuppressive roles in the tumor microenvironment and are able to condition NK cells to become anergic. In this review, we will describe how NK cells react with different stromal cells in the tumor microenvironment. This will be followed by a discussion on the role of hypoxic stress in the regulation of NK cell functions. The aim of this review is to provide a better understanding of how the tumor microenvironment impairs NK cell functions, thereby limiting the use of NK cell-based therapy, and we will attempt to suggest more efficient tools to establish a more favorable tumor microenvironment to boost NK cell cytotoxicity and control tumor progression.

No MeSH data available.


Related in: MedlinePlus