Role of the Natural Immune System in Control of Primary Tumors and Metastasis

Herberman, Ronald B.; Gorelik, Elieser

doi:10.1007/978-1-4613-0715-0_1

Cited by 6 publications

(5 citation statements)

References 116 publications

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“…establishment phases of tumor metastasis. 20,21,40 Blood NK cells, through their direct cytotoxic capacity, prevent the spread of tumor cells in the intravascular phase by eliminating hematogenous tumor cell distribution. Furthermore, organ-associated NK cells can secrete cytokines in the microenvironment that may modulate tumor behavior and regulate subsequent antitumor responses by other cell types.…”

Section: Discussionmentioning

confidence: 99%

Defective antitumor responses in CX3CR1‐deficient mice

Fong

Combadière

et al. 2007

Intl Journal of Cancer

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Innate immunity is critically important for tumor surveillance and regulating tumor metastasis. Fractalkine (FKN, CX3CL1), operating through the receptor CX3CR1, is an effective chemoattractant and adhesion receptor for NK cells and monocytes, important constituents of the innate immune response. Previous studies have shown that over-expression of CX3CL1 by tumor cells enhances antitumor responses. However, since most tumors do not express CX3CL1, it remains unclear if CX3CL1/CX3CR1 has a role in tumor immunity in the absence of ligand over-expression. To determine the role of CX3CL1 and CX3CR1 in regulating antitumor immune responses, we tested the response of wildtype and CX3CR1-deficient animals to unmanipulated B16 melanoma that does not express CX3CL1. We studied the distribution and trafficking of mononuclear cells (MNC) under homeostatic conditions and in the presence of B16 metastatic melanoma, cytotoxic activity, and cytokine production in wild-type and CX3CR1-deficient animals. We found that B16-treated CX3CR12/2 mice had increased lung tumor burden and cachexia. There was a selective reduction of monocytes and NK cells in the lungs of CX3CR1-deficient animals under homeostatic conditions and in response to B16. CX3CR1-deficient NK cells effectively killed B16 cells in cytotoxicity assays. However, CX3CR1-deficient NK cells exhibited a tumorigenic cytokine production profile with defective IFN-c expression and enhanced IL-6 production in response to TLR3 activation with polyIC. Our studies indicate that CX3CR1 is an important contributor to innate immunity at multiple levels. Its role in tumor immunity is not limited by expression of CX3CL1 by tumor cells. ' 2007 Wiley-Liss, Inc.Key words: CX3CR1; monocytes; NK cells; migration Anticancer immunity relies on the redistribution of leukocyte subsets to the developing tumor. Chemokines and their receptors are intimately involved in regulating organ-specific leukocyte trafficking and inflammation, and they have been implicated to play important roles in regulating cancer growth and metastasis.1,2 CX3CR1, the receptor for fractalkine (CX3CL1: fractalkine or FKN in man, and neurotactin or NTN in mouse), is expressed by many leukocyte cell types, including subsets of NK cells and monocytes, both of which are important for effective immunosurveillance against tumor growth and metastasis.3-6 CX3CL1, the only known member of the CX3C chemokine subfamily, is constitutively expressed at low levels on many epithelial cells, including lung, intestine, and skin, and is upregulated on activated endothelia and epithelia.3,7-9 Importantly, CX3CL1 expression in bronchial epithelium is dramatically upregulated by underlying cancer suggesting that CX3CL1 may be involved in the pathophysiology of cancer growth and metastasis, particularly in the lung.

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Section: Discussionmentioning

confidence: 99%

Defective antitumor responses in CX3CR1‐deficient mice

Fong

Combadière

et al. 2007

Intl Journal of Cancer

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“…Taking advantage of the selective NK cell deficiency in Tg mice, we evaluated the role of NK1.1 ϩ CD3 Ϫ NK cells in tumor rejection using two established in vivo tumor models (37). When B16 cells were i.v.…”

Section: Role Of Nk Cells In Suppression Of Tumor Metastasis and Outgmentioning

confidence: 99%

In vivonatural killer cell activities revealed by natural killer cell-deficient mice

Kim

Iizuka

Aguila

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

390

287

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“…It is well known that LGL possess a lytic activity against neoplastic and viral-infected cells, and also that they play a role in resistance to bacterial infections [24,25]. It is therefore important to evaluate the possible effect of meropenem on the main function of LGL, i.e.…”

Section: Discussionmentioning

confidence: 99%

In vitro Effects of Meropenem and Imipenem/Cilastatin on Some Functions of Human Natural Effector Cells

et al. 2000

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Meropenem, a new carbapenem antibiotic, was assessed to evaluate its effects on some functional parameters of human polymorphonuclear (PMN) and natural killer (NK) cells in comparison with imipenem/cilastatin. Both drugs significantly inhibited PMN phagocytosis and chemotaxis at concentrations of 2,000 and 4,000 μg/ml. They affected PMN microbicidal activity, evaluated against Candida albicans, only at 4,000 μg/ml. A study of the effects of both drugs on peripheral NK populations and the human NK line (NK-92) showed that even at 4,000 μg/ml there was no effect on antitumor activity. These data indicate that meropenem can reduce some PMN antimicrobial functions only at very high concentrations like imipenem/cilastatin, whereas no concentration influenced NK activity.

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Role of the Natural Immune System in Control of Primary Tumors and Metastasis

Cited by 6 publications

References 116 publications

Defective antitumor responses in CX3CR1‐deficient mice

Defective antitumor responses in CX3CR1‐deficient mice

In vivonatural killer cell activities revealed by natural killer cell-deficient mice

In vitro Effects of Meropenem and Imipenem/Cilastatin on Some Functions of Human Natural Effector Cells

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