Journal Mobile Options
Table of Contents
Vol. 86, No. 3, 2013
Issue release date: September 2013
Respiration 2013;86:216-223

Native Soluble Carcinoembryonic Antigen Is Not Involved in the Impaired Activity of CD56dim Natural Killer Cells in Malignant Pleural Effusion

Qi J. · Li D. · Feng J. · Yang S. · Su Y. · Fang M. · Tan Z. · Shi H. · Yan X. · Gong F. · Zheng F.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background: Natural killer (NK) cells are lymphocytes of the innate immune system that play a crucial role in tumor immune surveillance. Accumulated data indicated that NK cells in the tumor microenvironment often display a suppressed function. However, the mechanism is not clear. Objective: In this study, the effects and relative mechanisms of malignant pleural effusion (MPE) from patients with lung cancer on NK cells were researched. Methods: MPE and peripheral blood (PB) samples were collected from patients with lung cancer. The cytotoxic activity of CD56dim NK cells in PB and MPE mononuclear cells was analyzed by flow cytometry. Results: It was observed that the percentages of total NK cells and a CD56dim NK subset in MPE reduced accompanying impaired cytotoxic activity compared with that in paired PB. Cell-free MPE treatment reduced both the proportion and cytotoxic activity of CD56dim NK cells in PB from healthy donors. The suppression effects were not based on soluble carcinoembryonic antigen and the inhibitory cytokines interleukin-10 and transforming growth factor-β1, but were dependent on the factor with a molecular weight >100 kDa. Conclusions: These results demonstrated that native soluble carcinoembryonic antigen does not suppress the activity of NK cells, and an unknown factor with a molecular weight >100 kDa plays a critical role in the impairment of CD56dim NK cells in MPE, which might lead to tumor progression.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Thompson JA, Grunert F, Zimmermann W: Carcinoembryonic antigen gene family: molecular biology and clinical perspectives. J Clin Lab Anal 1991;5:344-366.
  2. Zheng C, Feng J, Lu D, Wang P, Xing S, Coll JL, Yang D, Yan X: A novel anti-CEACAM5 monoclonal antibody, CC4, suppresses colorectal tumor growth and enhances NK cells-mediated tumor immunity. PLoS One 2011;6:e21146.
  3. Hostetter RB, Campbell DE, Chi KF, Kerckhoff S, Cleary KR, Ullrich S, Thomas P, Jessup JM: Carcinoembryonic antigen enhances metastatic potential of human colorectal carcinoma. Arch Surg 1990;125:300-304.
  4. Cooper MA, Fehniger TA, Caligiuri MA: The biology of human natural killer-cell subsets. Trends Immunol 2001;22:633-640.
  5. Cooper MA, Fehniger TA, Turner SC, Chen KS, Ghaheri BA, Ghayur T, Carson WE, Caligiuri MA: Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset. Blood 2001;97:3146-3151.
  6. Stern N, Markel G, Arnon TI, Gruda R, Wong H, Gray-Owen SD, Mandelboim O: Carcinoembryonic antigen (CEA) inhibits NK killing via interaction with CEA-related cell adhesion molecule 1. J Immunol 2005;174:6692-6701.

    External Resources

  7. Gompelmann D, Eberhardt R, Herth FJF: Advanced malignant lung disease: what the specialist can offer. Respiration 2011;82:111-123.
  8. Blanchard DK, Kavanagh JJ, Sinkovics JG, Cavanagh D, Hewitt SM, Djeu JY: Infiltration of interleukin-2-inducible killer cells in ascitic fluid and pleural effusions of advanced cancer patients. Cancer Res 1988;48:6321-6327.

    External Resources

  9. Okubo Y, Nakata M, Kuroiwa Y, Wada S, Kusama S: NK cells in carcinomatous and tuberculous pleurisy. Phenotypic and functional analyses of NK cells in peripheral blood and pleural effusions. Chest 1987;92:500-504.
  10. Ye ZJ, Zhou Q, Gu YY, Qin SM, Ma WL, Xin JB, Tao XN, Shi HZ: Generation and differentiation of IL-17-producing CD4+ T cells in malignant pleural effusion. J Immunol 2010;185:6348-6354.
  11. Chen YM, Yang WK, Whang-Peng J, Kuo BI, Perng RP: Elevation of interleukin-10 levels in malignant pleural effusion. Chest 1996;110:433-436.
  12. Froudarakis ME: Pleural effusion in lung cancer: more questions than answers. Respiration 2012;83:367-376.
  13. Cai L, Zhang Z, Zhou L, Wang H, Fu J, Zhang S, Shi M, Zhang H, Yang Y, Wu H, Tien P, Wang FS: Functional impairment in circulating and intrahepatic NK cells and relative mechanism in hepatocellular carcinoma patients. Clin Immunol 2008;129:428-437.
  14. Schierloh P, Yokobori N, Aleman M, Musella RM, Beigier-Bompadre M, Saab MA, Alves L, Abbate E, de la Barrera SS, Sasiain MC: Increased susceptibility to apoptosis of CD56dimCD16+ NK cells induces the enrichment of IFN-gamma-producing CD56bright cells in tuberculous pleurisy. J Immunol 2005;175:6852-6860.

    External Resources

  15. Belisle JA, Gubbels JA, Raphael CA, Migneault M, Rancourt C, Connor JP, Patankar MS: Peritoneal natural killer cells from epithelial ovarian cancer patients show an altered phenotype and bind to the tumour marker MUC16 (CA125). Immunology 2007;122:418-429.
  16. Drake PM, Gunn MD, Charo IF, Tsou CL, Zhou Y, Huang L, Fisher SJ: Human placental cytotrophoblasts attract monocytes and CD56(bright) natural killer cells via the actions of monocyte inflammatory protein 1alpha. J Exp Med 2001;193:1199-1212.
  17. Pokkali S, Das SD, Selvaraj A: Differential upregulation of chemokine receptors on CD56 NK cells and their transmigration to the site of infection in tuberculous pleurisy. FEMS Immunol Med Microbiol 2009;55:352-360.
  18. Alter G, Malenfant JM, Altfeld M: CD107a as a functional marker for the identification of natural killer cell activity. J Immunol Methods 2004;294:15-22.
  19. Stern-Ginossar N, Nedvetzki S, Markel G, Gazit R, Betser-Cohen G, Achdout H, Aker M, Blumberg RS, Davis DM, Appelmelk B, Mandelboim O: Intercellular transfer of carcinoembryonic antigen from tumor cells to NK cells. J Immunol 2007;179:4424-4434.

    External Resources

  20. Garcia M, Seigner C, Bastid C, Choux R, Payan MJ, Reggio H: Carcinoembryonic antigen has a different molecular weight in normal colon and in cancer cells due to N-glycosylation differences. Cancer Res 1991;51:5679-5686.

    External Resources

  21. Atanackovic D, Cao Y, Kim JW, Brandl S, Thom I, Faltz C, Hildebrandt Y, Bartels K, de Weerth A, Hegewisch-Becker S, Hossfeld DK, Bokemeyer C: The local cytokine and chemokine milieu within malignant effusions. Tumour Biol 2008;29:93-104.
  22. Lee JC, Lee KM, Kim DW, Heo DS: Elevated TGF-beta1 secretion and down-modulation of NKG2D underlies impaired NK cytotoxicity in cancer patients. J Immunol 2004;172:7335-7340.

    External Resources

  23. Mitani K, Nishioka Y, Yamabe K, Ogawa H, Miki T, Yanagawa H, Sone S: Soluble Fas in malignant pleural effusion and its expression in lung cancer cells. Cancer Sci 2003;94:302-307.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50