Skip to main content
Top
Published in: Cancer Immunology, Immunotherapy 8/2007

01-08-2007 | Original Article

NK cells rapidly remove B16F10 tumor cells in a perforin and interferon-gamma independent manner in vivo

Authors: Martin A. Grundy, Tong Zhang, Charles L. Sentman

Published in: Cancer Immunology, Immunotherapy | Issue 8/2007

Login to get access

Abstract

Natural killer (NK) cells have been shown critical in reducing tumor lung metastasis in various murine cancer models. Effector molecules such as perforin and IFN-γ may play important roles in inhibition of metastasis. However, most of these conclusions were based on experiments that involved quantitation of metastatic colonies several weeks after tumor challenge. The roles of NK cells and their effector molecules (perforin and IFN-γ) in the initial immune responses against tumor metastasis in lungs are still unknown. By using the B16F10 melanoma tumor model combined with confocal microscopy, we observed an increase in numbers of B16F10 cells in NK-depleted mice at 60 min post tumor inoculation, but this effect was independent of perforin or IFN-γ. In addition, NK cell numbers in lungs after tumor injection rapidly increased suggesting a redistribution of NK cells in the lungs. However, NK cells were not found in contact with tumor cells until day 6 or later. Our data indicate that during early responses against B16F10 cells, NK cells use another mechanism(s) besides perforin and IFN-γ to prevent tumor metastasis.
Literature
2.
go back to reference Kuppen PJ, Gorter A, Hagenaars M, Jonges LE, Giezeman-Smits KM, Nagelkerke JF, Fleuren G, van de Velde CJ (2001) Role of NK cells in adoptive immunotherapy of metastatic colorectal cancer in a syngeneic rat model. Immunol Rev 184:236–243PubMedCrossRef Kuppen PJ, Gorter A, Hagenaars M, Jonges LE, Giezeman-Smits KM, Nagelkerke JF, Fleuren G, van de Velde CJ (2001) Role of NK cells in adoptive immunotherapy of metastatic colorectal cancer in a syngeneic rat model. Immunol Rev 184:236–243PubMedCrossRef
3.
go back to reference Kim S, Iizuka K, Aguila HL, Weissman IL, Yokoyama WM (2000) In vivo natural killer cell activities revealed by natural killer cell-deficient mice. Proc Natl Acad Sci USA 97:2731–2736PubMedCrossRef Kim S, Iizuka K, Aguila HL, Weissman IL, Yokoyama WM (2000) In vivo natural killer cell activities revealed by natural killer cell-deficient mice. Proc Natl Acad Sci USA 97:2731–2736PubMedCrossRef
4.
go back to reference Street SE, Cretney E, Smyth MJ (2001) Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 97:192–197PubMedCrossRef Street SE, Cretney E, Smyth MJ (2001) Perforin and interferon-gamma activities independently control tumor initiation, growth, and metastasis. Blood 97:192–197PubMedCrossRef
5.
go back to reference Takaki R, Hayakawa Y, Nelson A, Sivakumar PV, Hughes S, Smyth MJ, Lanier LL (2005) IL-21 enhances tumor rejection through a NKG2D-dependent mechanism. J Immunol 175:2167–2173PubMed Takaki R, Hayakawa Y, Nelson A, Sivakumar PV, Hughes S, Smyth MJ, Lanier LL (2005) IL-21 enhances tumor rejection through a NKG2D-dependent mechanism. J Immunol 175:2167–2173PubMed
6.
go back to reference Smyth MJ, Taniguchi M, Street SE (2000) The anti-tumor activity of IL-12: mechanisms of innate immunity that are model and dose dependent. J Immunol 165:2665–2670PubMed Smyth MJ, Taniguchi M, Street SE (2000) The anti-tumor activity of IL-12: mechanisms of innate immunity that are model and dose dependent. J Immunol 165:2665–2670PubMed
7.
go back to reference Hashimoto W, Tanaka F, Robbins PD, Taniguchi M, Okamura H, Lotze MT, Tahara H (2003) Natural killer, but not natural killer T, cells play a necessary role in the promotion of an innate antitumor response induced by IL-18. Int J Cancer 103:508–513PubMedCrossRef Hashimoto W, Tanaka F, Robbins PD, Taniguchi M, Okamura H, Lotze MT, Tahara H (2003) Natural killer, but not natural killer T, cells play a necessary role in the promotion of an innate antitumor response induced by IL-18. Int J Cancer 103:508–513PubMedCrossRef
8.
go back to reference Fidler IJ (2003) The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 3:453–458PubMedCrossRef Fidler IJ (2003) The pathogenesis of cancer metastasis: the ‘seed and soil’ hypothesis revisited. Nat Rev Cancer 3:453–458PubMedCrossRef
9.
go back to reference Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563–572PubMedCrossRef Chambers AF, Groom AC, MacDonald IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2:563–572PubMedCrossRef
10.
go back to reference Weis S, Cui J, Barnes L, Cheresh D (2004) Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor cell extravasation and metastasis. J Cell Biol 167:223–229PubMedCrossRef Weis S, Cui J, Barnes L, Cheresh D (2004) Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor cell extravasation and metastasis. J Cell Biol 167:223–229PubMedCrossRef
11.
go back to reference Cameron MD, Schmidt EE, Kerkvliet N, Nadkarni KV, Morris VL, Groom AC, Chambers AF, MacDonald IC (2000) Temporal progression of metastasis in lung: cell survival, dormancy, and location dependence of metastatic inefficiency. Cancer Res 60:2541–2546PubMed Cameron MD, Schmidt EE, Kerkvliet N, Nadkarni KV, Morris VL, Groom AC, Chambers AF, MacDonald IC (2000) Temporal progression of metastasis in lung: cell survival, dormancy, and location dependence of metastatic inefficiency. Cancer Res 60:2541–2546PubMed
12.
13.
go back to reference Liang S, Slattery MJ, Dong C (2005) Shear stress and shear rate differentially affect the multi-step process of leukocyte-facilitated melanoma adhesion. Exp Cell Res 310:282–292PubMedCrossRef Liang S, Slattery MJ, Dong C (2005) Shear stress and shear rate differentially affect the multi-step process of leukocyte-facilitated melanoma adhesion. Exp Cell Res 310:282–292PubMedCrossRef
14.
go back to reference Zhang T, Barber A, Sentman CL (2006) Generation of antitumor responses by genetic modification of primary human T cells with a chimeric NKG2D receptor. Cancer Res 66:5927–5933PubMedCrossRef Zhang T, Barber A, Sentman CL (2006) Generation of antitumor responses by genetic modification of primary human T cells with a chimeric NKG2D receptor. Cancer Res 66:5927–5933PubMedCrossRef
15.
go back to reference Sentman CL, Olsson MY, Salcedo M, Hoglund P, Lendahl U, Karre K (1994) H-2 allele-specific protection from NK cell lysis in vitro for lymphoblasts but not tumor targets. Protection mediated by alpha 1/alpha 2 domains. J Immunol 153:5482–5490PubMed Sentman CL, Olsson MY, Salcedo M, Hoglund P, Lendahl U, Karre K (1994) H-2 allele-specific protection from NK cell lysis in vitro for lymphoblasts but not tumor targets. Protection mediated by alpha 1/alpha 2 domains. J Immunol 153:5482–5490PubMed
16.
go back to reference Eriksson M, Leitz G, Fallman E, Axner O, Ryan JC, Nakamura MC, Sentman CL (1999) Inhibitory receptors alter natural killer cell interactions with target cells yet allow simultaneous killing of susceptible targets. J Exp Med 190:1005–1012PubMedCrossRef Eriksson M, Leitz G, Fallman E, Axner O, Ryan JC, Nakamura MC, Sentman CL (1999) Inhibitory receptors alter natural killer cell interactions with target cells yet allow simultaneous killing of susceptible targets. J Exp Med 190:1005–1012PubMedCrossRef
17.
go back to reference Chadwick BS, Miller RG (1992) Hybrid resistance in vitro. Possible role of both class I MHC and self peptides in determining the level of target cell sensitivity. J Immunol 148:2307–2313PubMed Chadwick BS, Miller RG (1992) Hybrid resistance in vitro. Possible role of both class I MHC and self peptides in determining the level of target cell sensitivity. J Immunol 148:2307–2313PubMed
18.
go back to reference Fahlen L, Lendahl U, Sentman CL (2001) MHC class I-Ly49 interactions shape the Ly49 repertoire on murine NK cells. J Immunol 166:6585–6592PubMed Fahlen L, Lendahl U, Sentman CL (2001) MHC class I-Ly49 interactions shape the Ly49 repertoire on murine NK cells. J Immunol 166:6585–6592PubMed
19.
go back to reference Grundy M, Sentman CL (2005) GFP transgenic mice show dynamics of lung macrophages. Exp Cell Res 310:409–416PubMedCrossRef Grundy M, Sentman CL (2005) GFP transgenic mice show dynamics of lung macrophages. Exp Cell Res 310:409–416PubMedCrossRef
20.
go back to reference Shingu K, Helfritz A, Kuhlmann S, Zielinska-Skowronek M, Jacobs R, Schmidt RE, Pabst R, von Horsten S (2002) Kinetics of the early recruitment of leukocyte subsets at the sites of tumor cells in the lungs: natural killer (NK) cells rapidly attract monocytes but not lymphocytes in the surveillance of micrometastasis. Int J Cancer 99:74–81PubMedCrossRef Shingu K, Helfritz A, Kuhlmann S, Zielinska-Skowronek M, Jacobs R, Schmidt RE, Pabst R, von Horsten S (2002) Kinetics of the early recruitment of leukocyte subsets at the sites of tumor cells in the lungs: natural killer (NK) cells rapidly attract monocytes but not lymphocytes in the surveillance of micrometastasis. Int J Cancer 99:74–81PubMedCrossRef
21.
go back to reference Al-Mehdi AB, Tozawa K, Fisher AB, Shientag L, Lee A, Muschel RJ (2000) Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nat Med 6:100–102PubMedCrossRef Al-Mehdi AB, Tozawa K, Fisher AB, Shientag L, Lee A, Muschel RJ (2000) Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nat Med 6:100–102PubMedCrossRef
22.
go back to reference Yu YY, George T, Dorfman JR, Roland J, Kumar V, Bennett M (1996) The role of Ly49A and 5E6(Ly49C) molecules in hybrid resistance mediated by murine natural killer cells against normal T cell blasts. Immunity 4:67–76PubMedCrossRef Yu YY, George T, Dorfman JR, Roland J, Kumar V, Bennett M (1996) The role of Ly49A and 5E6(Ly49C) molecules in hybrid resistance mediated by murine natural killer cells against normal T cell blasts. Immunity 4:67–76PubMedCrossRef
23.
go back to reference Hoffman RM (2005) The multiple uses of fluorescent proteins to visualize cancer in vivo. Nat Rev Cancer 5:796–806PubMedCrossRef Hoffman RM (2005) The multiple uses of fluorescent proteins to visualize cancer in vivo. Nat Rev Cancer 5:796–806PubMedCrossRef
24.
go back to reference Yamamoto N, Jiang P, Yang M, Xu M, Yamauchi K, Tsuchiya H, Tomita K, Wahl GM, Moossa AR, Hoffman RM (2004) Cellular dynamics visualized in live cells in vitro and in vivo by differential dual-color nuclear-cytoplasmic fluorescent-protein expression. Cancer Res 64:4251–4256PubMedCrossRef Yamamoto N, Jiang P, Yang M, Xu M, Yamauchi K, Tsuchiya H, Tomita K, Wahl GM, Moossa AR, Hoffman RM (2004) Cellular dynamics visualized in live cells in vitro and in vivo by differential dual-color nuclear-cytoplasmic fluorescent-protein expression. Cancer Res 64:4251–4256PubMedCrossRef
25.
go back to reference Yamauchi K, Yang M, Jiang P, Yamamoto N, Xu M, Amoh Y, Tsuji K, Bouvet M, Tsuchiya H, Tomita K, Moossa AR, Hoffman RM (2005) Real-time in vivo dual-color imaging of intracapillary cancer cell and nucleus deformation and migration. Cancer Res 65:4246–4252PubMedCrossRef Yamauchi K, Yang M, Jiang P, Yamamoto N, Xu M, Amoh Y, Tsuji K, Bouvet M, Tsuchiya H, Tomita K, Moossa AR, Hoffman RM (2005) Real-time in vivo dual-color imaging of intracapillary cancer cell and nucleus deformation and migration. Cancer Res 65:4246–4252PubMedCrossRef
26.
go back to reference Wong CW, Song C, Grimes MM, Fu W, Dewhirst MW, Muschel RJ, Al-Mehdi AB (2002) Intravascular location of breast cancer cells after spontaneous metastasis to the lung. Am J Pathol 161:749–753PubMed Wong CW, Song C, Grimes MM, Fu W, Dewhirst MW, Muschel RJ, Al-Mehdi AB (2002) Intravascular location of breast cancer cells after spontaneous metastasis to the lung. Am J Pathol 161:749–753PubMed
27.
go back to reference Holt PG, Degebrodt A, Venaille T, O’Leary C, Krska K, Flexman J, Farrell H, Shellam G, Young P, Penhale J, Robertson T, Papadimitriou JM (1985) Preparation of interstitial lung cells by enzymatic digestion of tissue slices: preliminary characterization by morphology and performance in functional assays. Immunology 54:139–147PubMed Holt PG, Degebrodt A, Venaille T, O’Leary C, Krska K, Flexman J, Farrell H, Shellam G, Young P, Penhale J, Robertson T, Papadimitriou JM (1985) Preparation of interstitial lung cells by enzymatic digestion of tissue slices: preliminary characterization by morphology and performance in functional assays. Immunology 54:139–147PubMed
28.
go back to reference Weissler JC, Nicod LP, Lipscomb MF, Toews GB (1987) Natural killer cell function in human lung is compartmentalized. Am Rev Respir Dis 135:941–949PubMed Weissler JC, Nicod LP, Lipscomb MF, Toews GB (1987) Natural killer cell function in human lung is compartmentalized. Am Rev Respir Dis 135:941–949PubMed
29.
go back to reference Prichard MG, Boerth LW, Pennington JE (1987) Compartmental analysis of resting and activated pulmonary natural killer cells. Exp Lung Res 12:239–251PubMed Prichard MG, Boerth LW, Pennington JE (1987) Compartmental analysis of resting and activated pulmonary natural killer cells. Exp Lung Res 12:239–251PubMed
30.
go back to reference Wiltrout RH, Herberman RB, Zhang SR, Chirigos MA, Ortaldo JR, Green KM Jr, Talmadge JE (1985) Role of organ-associated NK cells in decreased formation of experimental metastases in lung and liver. J Immunol 134:4267–4275PubMed Wiltrout RH, Herberman RB, Zhang SR, Chirigos MA, Ortaldo JR, Green KM Jr, Talmadge JE (1985) Role of organ-associated NK cells in decreased formation of experimental metastases in lung and liver. J Immunol 134:4267–4275PubMed
31.
go back to reference Li CY, Shan S, Huang Q, Braun RD, Lanzen J, Hu K, Lin P, Dewhirst MW (2000) Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models. J Natl Cancer Inst 92:143–147PubMedCrossRef Li CY, Shan S, Huang Q, Braun RD, Lanzen J, Hu K, Lin P, Dewhirst MW (2000) Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models. J Natl Cancer Inst 92:143–147PubMedCrossRef
32.
go back to reference Smyth MJ, Thia KY, Street SE, Cretney E, Trapani JA, Taniguchi M, Kawano T, Pelikan SB, Crowe NY, Godfrey DI (2000) Differential tumor surveillance by natural killer (NK) and NKT cells. J Exp Med 191:661–668PubMedCrossRef Smyth MJ, Thia KY, Street SE, Cretney E, Trapani JA, Taniguchi M, Kawano T, Pelikan SB, Crowe NY, Godfrey DI (2000) Differential tumor surveillance by natural killer (NK) and NKT cells. J Exp Med 191:661–668PubMedCrossRef
33.
go back to reference Kayagaki N, Yamaguchi N, Nakayama M, Takeda K, Akiba H, Tsutsui H, Okamura H, Nakanishi K, Okumura K, Yagita H (1999) Expression and function of TNF-related apoptosis-inducing ligand on murine activated NK cells. J Immunol 163:1906–1913PubMed Kayagaki N, Yamaguchi N, Nakayama M, Takeda K, Akiba H, Tsutsui H, Okamura H, Nakanishi K, Okumura K, Yagita H (1999) Expression and function of TNF-related apoptosis-inducing ligand on murine activated NK cells. J Immunol 163:1906–1913PubMed
34.
go back to reference Taieb J, Chaput N, Menard C, Apetoh L, Ullrich E, Bonmort M, Pequignot M, Casares N, Terme M, Flament C, Opolon P, Lecluse Y, Metivier D, Tomasello E, Vivier E, Ghiringhelli F, Martin F, Klatzmann D, Poynard T, Tursz T, Raposo G, Yagita H, Ryffel B, Kroemer G, Zitvogel L (2006) A novel dendritic cell subset involved in tumor immunosurveillance. Nat Med 12:214–219PubMedCrossRef Taieb J, Chaput N, Menard C, Apetoh L, Ullrich E, Bonmort M, Pequignot M, Casares N, Terme M, Flament C, Opolon P, Lecluse Y, Metivier D, Tomasello E, Vivier E, Ghiringhelli F, Martin F, Klatzmann D, Poynard T, Tursz T, Raposo G, Yagita H, Ryffel B, Kroemer G, Zitvogel L (2006) A novel dendritic cell subset involved in tumor immunosurveillance. Nat Med 12:214–219PubMedCrossRef
35.
go back to reference Chan CW, Crafton E, Fan HN, Flook J, Yoshimura K, Skarica M, Brockstedt D, Dubensky TW, Stins MF, Lanier LL, Pardoll DM, Housseau F (2006) Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity. Nat Med 12:207–213PubMedCrossRef Chan CW, Crafton E, Fan HN, Flook J, Yoshimura K, Skarica M, Brockstedt D, Dubensky TW, Stins MF, Lanier LL, Pardoll DM, Housseau F (2006) Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity. Nat Med 12:207–213PubMedCrossRef
Metadata
Title
NK cells rapidly remove B16F10 tumor cells in a perforin and interferon-gamma independent manner in vivo
Authors
Martin A. Grundy
Tong Zhang
Charles L. Sentman
Publication date
01-08-2007
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 8/2007
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-006-0264-1

Other articles of this Issue 8/2007

Cancer Immunology, Immunotherapy 8/2007 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine