CEACAM1-3S Drives Melanoma Cells into NK Cell-Mediated Cytolysis and Enhances Patient Survival

Cancer Research
Nico UllrichIris Helfrich

Abstract

CEACAM1 is a widely expressed multifunctional cell-cell adhesion protein reported to serve as a poor prognosis marker in melanoma patients. In this study, we examine the functional and clinical contributions of the four splice isoforms of CEACAM1. Specifically, we present in vitro and in vivo evidence that they affect melanoma progression and immune surveillance in a negative or positive manner that is isoform specific in action. In contrast with isoforms CEACAM1-4S and CEACAM1-4L, expression of isoforms CEACAM1-3S and CEACAM1-3L is induced during disease progression shown to correlate with clinical stage. Unexpectedly, overall survival was prolonged in patients with advanced melanomas expressing CEACAM1-3S. The favorable effects of CEACAM1-3S related to enhanced immunogenicity, which was mediated by cell surface upregulation of NKG2D receptor ligands, thereby sensitizing melanoma cells to lysis by natural killer cells. Conversely, CEACAM1-4L downregulated cell surface levels of the NKG2D ligands MICA and ULBP2 by enhanced shedding, thereby promoting malignant character. Overall, our results define the splice isoform-specific immunomodulatory and cell biologic functions of CEACAM1 in melanoma pathogenesis.

References

Jan 1, 1991·Journal of Clinical Laboratory Analysis·J A ThompsonW Zimmermann
Nov 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·M NeumaierC Wagener
Jul 1, 1997·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·L RiethdorfT Löning
Jul 27, 1999·Cancer Gene Therapy·W LuoS H Lin
Aug 15, 2001·Experimental Cell Research·N BeaucheminW Zimmermann
Mar 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gal MarkelOfer Mandelboim
May 16, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Anka ThiesUdo Schumacher
Oct 29, 2004·The American Journal of Pathology·Alireza EbrahimnejadJens Brümmer
May 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Noam SternOfer Mandelboim
May 24, 2005·European Journal of Immunology·Bernhard B SingerLothar Lucka
May 26, 2006·Nature Reviews. Immunology·Scott D Gray-Owen, Richard S Blumberg
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gal MarkelJacob Schachter
May 9, 2008·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Björn Obrink
Oct 7, 2008·Oncogene·N Nausch, A Cerwenka
May 23, 2009·American Journal of Clinical Pathology·Thilo GambichlerAlexander Kreuter
Jul 25, 2009·Journal of Experimental & Clinical Cancer Research : CR·Zeng Feng XinSung Taek Jung
Jul 28, 2009·Cancer Immunology, Immunotherapy : CII·Gal MarkelJacob Schachter
Nov 18, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Charles M BalchVernon K Sondak
Mar 9, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gang LiuJennifer D Wu
Jun 12, 2010·Immunological Reviews·Marine Champsaur, Lewis L Lanier
Jan 13, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Giulia FregniAnne Caignard
Dec 7, 2011·The Journal of Experimental Medicine·Zhangguo ChenRichard S Blumberg
Dec 27, 2011·Current Topics in Medicinal Chemistry·S SapoznikG Markel
Feb 1, 2012·Clinical & Developmental Immunology·Sapoznik SivanLotem Michal
Jul 4, 2012·Annali Dell'Istituto Superiore Di Sanità·Valentina FioriMaurizio Cianfriglia
Oct 16, 2012·The American Journal of Pathology·Laurie A Shuman MossWilliam G Stetler-Stevenson
Jan 15, 2014·Nature Reviews. Clinical Oncology·Dirk Schadendorf, Axel Hauschild

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Citations

Jun 18, 2015·Cancer Metastasis Reviews·Ye LingWang Xiang-dong
Feb 14, 2018·Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery·Kenric TamJohn B Sunwoo
Nov 6, 2015·Frontiers in Oncology·Stefanie LöffekIris Helfrich
Oct 21, 2016·Expert Opinion on Pharmacotherapy·Rossella MartinelloFilippo Montemurro
Oct 25, 2016·Future Medicinal Chemistry·Tinghan LiZhiyu Li
Jul 28, 2018·Disease Markers·Leticia Oliveira-FerrerKarin Milde-Langosch
Nov 18, 2015·Pigment Cell & Melanoma Research·Li Pan, Ling Hou
Nov 9, 2018·Journal of Immunology Research·Andreea CalinescuIoana A Badarau
Aug 16, 2017·Oncoimmunology·Matthew DanknerNicole Beauchemin
Oct 3, 2020·Molecular Cancer Research : MCR·Jessica A SmartEdward J Hartsough
Feb 7, 2020·Biochemistry and Biophysics Reports·Soichiro HayashiSiro Simizu

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