Melanoma-associated fibroblasts modulate NK cell phenotype and antitumor cytotoxicity.

Proceedings of the National Academy of Sciences of the United States of America
Mirna BalsamoMassimo Vitale

Abstract

Although the role of the tumor microenvironment in the process of cancer progression has been extensively investigated, the contribution of different stromal components to tumor growth and/or evasion from immune surveillance is still only partially defined. In this study we analyzed fibroblasts derived from metastatic melanomas and provide evidence for their strong immunosuppressive activity. In coculture experiments, melanoma-derived fibroblasts sharply interfered with NK cell functions including cytotoxicity and cytokine production. Thus, both the IL-2-induced up-regulation of the surface expression of NKp44, NKp30, and DNAM-1 triggering receptors and the acquisition of cytolytic granules were inhibited in NK cells. This resulted in an impairment of the NK cell-mediated killing of melanoma target cells. Transwell cocultures and the use of specific inhibitors suggested that cell-to-cell contact was required for inducing DNAM-1 modulation. In contrast, modulation of NKp44 and NKp30 was due to PGE(2) released by fibroblasts during coculture. Normal skin fibroblasts could also partially affect NK cell phenotype and function. However, the inhibitory effect of tumor-derived fibroblasts was far stronger and directly correlated with ...Continue Reading

References

Jan 1, 1989·Advances in Immunology·G Trinchieri
Feb 1, 1995·Current Opinion in Immunology·P Scott, G Trinchieri
Nov 8, 2001·Trends in Immunology·M A CooperM A Caligiuri
Mar 22, 2002·Nature Reviews. Immunology·A Cerwenka, L L Lanier
Mar 21, 2003·Proceedings of the National Academy of Sciences of the United States of America·Roberta CastriconiAlessandro Moretta
May 6, 2003·European Journal of Immunology·Tobias SilzleLeoni A Kunz-Schughart
Nov 26, 2003·International Journal of Cancer. Journal International Du Cancer·Tobias SilzleLeoni A Kunz-Schughart
Dec 23, 2003·Cancer Biology & Therapy·A-C GouletMark A Nelson
Feb 18, 2004·Nature Reviews. Cancer·Ugo Cavallaro, Gerhard Christofori
Oct 21, 2004·Blood·Sudeepta Aggarwal, Mark F Pittenger
Nov 2, 2004·Nature Reviews. Cancer·Margareta M Mueller, Norbert E Fusenig
Nov 9, 2004·Trends in Immunology·Lorenzo MorettaAlessandro Moretta
Sep 6, 2005·Blood·Anna CorcioneAntonio Uccelli
Oct 4, 2005·Trends in Immunology·Alessandro MorettaLorenzo Moretta
Oct 6, 2005·The Journal of Experimental Medicine·Robbie B MailliardPawel Kalinski
Nov 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alessandro PoggiMaria Raffaella Zocchi
Mar 31, 2006·Nature Reviews. Cancer·Raghu Kalluri, Michael Zeisberg
Sep 16, 2006·Nature Reviews. Immunology·Laurence ZitvogelGuido Kroemer
Oct 24, 2006·Nature Immunology·Stefan WelteAlexander Steinle
Apr 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael R NazarethRichard B Bankert
Jun 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Antoni ChanPaul Bowness
Jul 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Muzlifah A HaniffaMatthew P Collin
Aug 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Simon JonesFrancesco Dazzi
Dec 7, 2007·The Journal of Allergy and Clinical Immunology·Francesca ScordamagliaMassimo Vitale
Apr 22, 2008·Nature Immunology·Eric VivierSophie Ugolini
Dec 18, 2008·International Immunology·Diederik van de WeteringEsther van de Vosse
Apr 8, 2009·The Journal of Clinical Investigation·Tadepally LakshmikanthFrancesco Colucci
May 12, 2009·Melanoma Research·Maria R BeckerTimo Gaiser

❮ Previous
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Citations

Aug 2, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jahan S KhaliliGregory Lizée
Apr 20, 2011·Journal of Innate Immunity·Ana Stojanovic, Adelheid Cerwenka
Dec 1, 2012·Immunotherapy·Sunitha KakarlaStephen Gottschalk
Mar 13, 2014·Seminars in Immunology·Franco LocatelliPietro Merli
Mar 25, 2014·Immunology Letters·Alessandro PoggiMaria Raffaella Zocchi
Jan 11, 2014·Seminars in Cancer Biology·James Harper, Richard C A Sainson
Apr 30, 2013·Cancer Immunology, Immunotherapy : CII·Jens H W PahlMarco W Schilham
Jul 30, 2014·The Journal of Experimental Medicine·Daniel ÖhlundDavid Tuveson
Nov 9, 2010·Annual Review of Physiology·D W PowellR C Mifflin
Jul 6, 2014·Journal of Mammary Gland Biology and Neoplasia·Ashleigh UnsworthKara Britt
Aug 13, 2013·Expert Opinion on Biological Therapy·Alexei ShimanovskyConstantin A Dasanu
Jul 31, 2012·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Kai WangYufeng Cheng
Jun 15, 2015·Biochimica Et Biophysica Acta·Anna JohanssonRuth Ganss
Oct 16, 2012·Pharmacology & Therapeutics·Jing Zhang, Jinsong Liu
Mar 10, 2010·Experimental Cell Research·Kristian Pietras, Arne Ostman
May 20, 2015·Immunology Letters·Paola VaccaMaria Cristina Mingari
May 8, 2013·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Elisa MontaldoLorenzo Moretta
Apr 30, 2014·European Journal of Immunology·Massimo VitaleLorenzo Moretta
Oct 17, 2015·Nature Reviews. Immunology·Shannon J TurleyJillian L Astarita
Sep 1, 2015·Immunotherapy·Claudia CantoniMassimo Vitale
Aug 21, 2015·Cancer Immunology, Immunotherapy : CII·Gabriella PietraLorenzo Moretta
Mar 24, 2016·Pharmacology & Therapeutics·Zhuo Li, Yibin Kang
Mar 31, 2015·Pigment Cell & Melanoma Research·Andrea Ladányi
Aug 6, 2015·Nanomedicine·Vaibhav MundraRam I Mahato
Nov 6, 2012·Biochimica Et Biophysica Acta·Timothy MarshSandra S McAllister
Jul 24, 2015·Cancer Immunology, Immunotherapy : CII·Hideyuki TakahashiKazuaki Chikamatsu
Oct 14, 2014·Cellular & Molecular Immunology·Cheng SunZhigang Tian
Dec 25, 2012·Oncoimmunology·Mirna BalsamoMassimo Vitale
Jan 28, 2015·The American Journal of Pathology·SuFey OngDaniela Čiháková
Mar 29, 2014·Frontiers in Immunology·Simona SivoriEmanuela Marcenaro
Mar 19, 2014·Frontiers in Immunology·Lorenzo MorettaMaria Cristina Mingari
Jun 18, 2016·Immunology Letters·Anamika BoseRathindranath Baral

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