Abstract
The dual properties of genetic instability and clonal expansion allow the development of a tumour to occur in a microevolutionary fashion. A broad range of pressures are exerted upon a tumour during neoplastic development. Such pressures are responsible for the selection of adaptations which provide a growth or survival advantage to the tumour. The nature of such selective pressures is implied in the phenotype of tumours that have undergone selection. We have reviewed a range of immunologically relevant adaptations that are frequently exhibited by common tumours. Many of these have the potential to function as mechanisms of immune response evasion by the tumour. Thus, such adaptations provide evidence for both the existence of immune surveillance, and the concept of immune selection in neoplastic development. This line of reasoning is supported by experimental evidence from murine models of immune involvement in neoplastic development. The process of immune selection has serious implications for the development of clinical immunotherapeutic strategies and our understanding of current in vivo models of tumour immunotherapy. © 2000 Cancer Research Campaign
Keywords: immune selection, evolution, tumour, immune escape
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- Ademmer K., Ebert M., Müller-Ostermeyer F., Friess H., Büchler M. W., Schubert W., Malfertheiner P. Effector T lymphocyte subsets in human pancreatic cancer: detection of CD8+CD18+ cells and CD8+CD103+ cells by multi-epitope imaging. Clin Exp Immunol. 1998 Apr;112(1):21–26. doi: 10.1046/j.1365-2249.1998.00546.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Agrawal B., Krantz M. J., Reddish M. A., Longenecker B. M. Cancer-associated MUC1 mucin inhibits human T-cell proliferation, which is reversible by IL-2. Nat Med. 1998 Jan;4(1):43–49. doi: 10.1038/nm0198-043. [DOI] [PubMed] [Google Scholar]
- Aizawa K., Ueki K., Suzuki S., Yabusaki H., Kanda T., Nishimaki T., Suzuki T., Hatakeyama K. Apoptosis and Bbcl-2 expression in gastric carcinomas: correlation withclinicopathological variables, p53 expression, cell proliferation and prognosis. Int J Oncol. 1999 Jan;14(1):85–91. doi: 10.3892/ijo.14.1.85. [DOI] [PubMed] [Google Scholar]
- Alexandroff A. B., Jackson A. M., O'Donnell M. A., James K. BCG immunotherapy of bladder cancer: 20 years on. Lancet. 1999 May 15;353(9165):1689–1694. doi: 10.1016/S0140-6736(98)07422-4. [DOI] [PubMed] [Google Scholar]
- Bennett M. W., O'connell J., O'sullivan G. C., Roche D., Brady C., Kelly J., Collins J. K., Shanahan F. Expression of Fas ligand by human gastric adenocarcinomas: a potential mechanism of immune escape in stomach cancer. Gut. 1999 Feb;44(2):156–162. doi: 10.1136/gut.44.2.156. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berke G. The CTL's kiss of death. Cell. 1995 Apr 7;81(1):9–12. doi: 10.1016/0092-8674(95)90365-8. [DOI] [PubMed] [Google Scholar]
- Boon T. Toward a genetic analysis of tumor rejection antigens. Adv Cancer Res. 1992;58:177–210. doi: 10.1016/s0065-230x(08)60295-x. [DOI] [PubMed] [Google Scholar]
- Cai Z., Bettaieb A., Mahdani N. E., Legrès L. G., Stancou R., Masliah J., Chouaib S. Alteration of the sphingomyelin/ceramide pathway is associated with resistance of human breast carcinoma MCF7 cells to tumor necrosis factor-alpha-mediated cytotoxicity. J Biol Chem. 1997 Mar 14;272(11):6918–6926. doi: 10.1074/jbc.272.11.6918. [DOI] [PubMed] [Google Scholar]
- Chen Y. T., Scanlan M. J., Sahin U., Türeci O., Gure A. O., Tsang S., Williamson B., Stockert E., Pfreundschuh M., Old L. J. A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1914–1918. doi: 10.1073/pnas.94.5.1914. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cheng J., Zhou T., Liu C., Shapiro J. P., Brauer M. J., Kiefer M. C., Barr P. J., Mountz J. D. Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science. 1994 Mar 25;263(5154):1759–1762. doi: 10.1126/science.7510905. [DOI] [PubMed] [Google Scholar]
- Chouaib S., Asselin-Paturel C., Mami-Chouaib F., Caignard A., Blay J. Y. The host-tumor immune conflict: from immunosuppression to resistance and destruction. Immunol Today. 1997 Oct;18(10):493–497. doi: 10.1016/s0167-5699(97)01115-8. [DOI] [PubMed] [Google Scholar]
- Christofori G., Semb H. The role of the cell-adhesion molecule E-cadherin as a tumour-suppressor gene. Trends Biochem Sci. 1999 Feb;24(2):73–76. doi: 10.1016/s0968-0004(98)01343-7. [DOI] [PubMed] [Google Scholar]
- Cox A. L., Skipper J., Chen Y., Henderson R. A., Darrow T. L., Shabanowitz J., Engelhard V. H., Hunt D. F., Slingluff C. L., Jr Identification of a peptide recognized by five melanoma-specific human cytotoxic T cell lines. Science. 1994 Apr 29;264(5159):716–719. doi: 10.1126/science.7513441. [DOI] [PubMed] [Google Scholar]
- Cromme F. V., van Bommel P. F., Walboomers J. M., Gallee M. P., Stern P. L., Kenemans P., Helmerhorst T. J., Stukart M. J., Meijer C. J. Differences in MHC and TAP-1 expression in cervical cancer lymph node metastases as compared with the primary tumours. Br J Cancer. 1994 Jun;69(6):1176–1181. doi: 10.1038/bjc.1994.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Eder I. E., Stenzl A., Hobisch A., Cronauer M. V., Bartsch G., Klocker H. Expression of transforming growth factors beta-1, beta 2 and beta 3 in human bladder carcinomas. Br J Cancer. 1997;75(12):1753–1760. doi: 10.1038/bjc.1997.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Engel A. M., Svane I. M., Rygaard J., Werdelin O. MCA sarcomas induced in scid mice are more immunogenic than MCA sarcomas induced in congenic, immunocompetent mice. Scand J Immunol. 1997 May;45(5):463–470. doi: 10.1046/j.1365-3083.1997.d01-419.x. [DOI] [PubMed] [Google Scholar]
- Fey M. F., Tobler A. Tumour heterogeneity and clonality--an old theme revisited. Ann Oncol. 1996 Feb;7(2):121–128. doi: 10.1093/oxfordjournals.annonc.a010537. [DOI] [PubMed] [Google Scholar]
- Fuchs E. J., Matzinger P. Is cancer dangerous to the immune system? Semin Immunol. 1996 Oct;8(5):271–280. doi: 10.1006/smim.1996.0035. [DOI] [PubMed] [Google Scholar]
- Gallucci S., Lolkema M., Matzinger P. Natural adjuvants: endogenous activators of dendritic cells. Nat Med. 1999 Nov;5(11):1249–1255. doi: 10.1038/15200. [DOI] [PubMed] [Google Scholar]
- Garrido F., Cabrera T., Concha A., Glew S., Ruiz-Cabello F., Stern P. L. Natural history of HLA expression during tumour development. Immunol Today. 1993 Oct;14(10):491–499. doi: 10.1016/0167-5699(93)90264-L. [DOI] [PubMed] [Google Scholar]
- Garrido F., Ruiz-Cabello F., Cabrera T., Pérez-Villar J. J., López-Botet M., Duggan-Keen M., Stern P. L. Implications for immunosurveillance of altered HLA class I phenotypes in human tumours. Immunol Today. 1997 Feb;18(2):89–95. doi: 10.1016/s0167-5699(96)10075-x. [DOI] [PubMed] [Google Scholar]
- Gastl G. A., Abrams J. S., Nanus D. M., Oosterkamp R., Silver J., Liu F., Chen M., Albino A. P., Bander N. H. Interleukin-10 production by human carcinoma cell lines and its relationship to interleukin-6 expression. Int J Cancer. 1993 Aug 19;55(1):96–101. doi: 10.1002/ijc.2910550118. [DOI] [PubMed] [Google Scholar]
- Hahne M., Rimoldi D., Schröter M., Romero P., Schreier M., French L. E., Schneider P., Bornand T., Fontana A., Lienard D. Melanoma cell expression of Fas(Apo-1/CD95) ligand: implications for tumor immune escape. Science. 1996 Nov 22;274(5291):1363–1366. doi: 10.1126/science.274.5291.1363. [DOI] [PubMed] [Google Scholar]
- Hu H. M., Urba W. J., Fox B. A. Gene-modified tumor vaccine with therapeutic potential shifts tumor-specific T cell response from a type 2 to a type 1 cytokine profile. J Immunol. 1998 Sep 15;161(6):3033–3041. [PubMed] [Google Scholar]
- Håkansson L., Adell G., Boeryd B., Sjögren F., Sjödahl R. Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis. Br J Cancer. 1997;75(3):374–380. doi: 10.1038/bjc.1997.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Irmler M., Thome M., Hahne M., Schneider P., Hofmann K., Steiner V., Bodmer J. L., Schröter M., Burns K., Mattmann C. Inhibition of death receptor signals by cellular FLIP. Nature. 1997 Jul 10;388(6638):190–195. doi: 10.1038/40657. [DOI] [PubMed] [Google Scholar]
- Janeway C. A., Jr, Goodnow C. C., Medzhitov R. Danger - pathogen on the premises! Immunological tolerance. Curr Biol. 1996 May 1;6(5):519–522. doi: 10.1016/s0960-9822(02)00531-6. [DOI] [PubMed] [Google Scholar]
- Jodo S., Kobayashi S., Nakajima Y., Matsunaga T., Nakayama N., Ogura N., Kayagaki N., Okumura K., Koike T. Elevated serum levels of soluble Fas/APO-1 (CD95) in patients with hepatocellular carcinoma. Clin Exp Immunol. 1998 May;112(2):166–171. doi: 10.1046/j.1365-2249.1998.00569.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Karecla P. I., Green S. J., Bowden S. J., Coadwell J., Kilshaw P. J. Identification of a binding site for integrin alphaEbeta7 in the N-terminal domain of E-cadherin. J Biol Chem. 1996 Nov 29;271(48):30909–30915. doi: 10.1074/jbc.271.48.30909. [DOI] [PubMed] [Google Scholar]
- Keating P. J., Cromme F. V., Duggan-Keen M., Snijders P. J., Walboomers J. M., Hunter R. D., Dyer P. A., Stern P. L. Frequency of down-regulation of individual HLA-A and -B alleles in cervical carcinomas in relation to TAP-1 expression. Br J Cancer. 1995 Aug;72(2):405–411. doi: 10.1038/bjc.1995.346. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kurokohchi K., Carrington M., Mann D. L., Simonis T. B., Alexander-Miller M. A., Feinstone S. M., Akatsuka T., Berzofsky J. A. Expression of HLA class I molecules and the transporter associated with antigen processing in hepatocellular carcinoma. Hepatology. 1996 May;23(5):1181–1188. doi: 10.1002/hep.510230537. [DOI] [PubMed] [Google Scholar]
- Lanier L. L. NK cell receptors. Annu Rev Immunol. 1998;16:359–393. doi: 10.1146/annurev.immunol.16.1.359. [DOI] [PubMed] [Google Scholar]
- Lee P. P., Yee C., Savage P. A., Fong L., Brockstedt D., Weber J. S., Johnson D., Swetter S., Thompson J., Greenberg P. D. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat Med. 1999 Jun;5(6):677–685. doi: 10.1038/9525. [DOI] [PubMed] [Google Scholar]
- Lehmann F., Marchand M., Hainaut P., Pouillart P., Sastre X., Ikeda H., Boon T., Coulie P. G. Differences in the antigens recognized by cytolytic T cells on two successive metastases of a melanoma patient are consistent with immune selection. Eur J Immunol. 1995 Feb;25(2):340–347. doi: 10.1002/eji.1830250206. [DOI] [PubMed] [Google Scholar]
- Lengauer C., Kinzler K. W., Vogelstein B. Genetic instabilities in human cancers. Nature. 1998 Dec 17;396(6712):643–649. doi: 10.1038/25292. [DOI] [PubMed] [Google Scholar]
- Ljunggren H. G., Stam N. J., Ohlén C., Neefjes J. J., Höglund P., Heemels M. T., Bastin J., Schumacher T. N., Townsend A., Kärre K. Empty MHC class I molecules come out in the cold. Nature. 1990 Aug 2;346(6283):476–480. doi: 10.1038/346476a0. [DOI] [PubMed] [Google Scholar]
- Maeda H., Shiraishi A. TGF-beta contributes to the shift toward Th2-type responses through direct and IL-10-mediated pathways in tumor-bearing mice. J Immunol. 1996 Jan 1;156(1):73–78. [PubMed] [Google Scholar]
- Maeurer M. J., Gollin S. M., Martin D., Swaney W., Bryant J., Castelli C., Robbins P., Parmiani G., Storkus W. J., Lotze M. T. Tumor escape from immune recognition: lethal recurrent melanoma in a patient associated with downregulation of the peptide transporter protein TAP-1 and loss of expression of the immunodominant MART-1/Melan-A antigen. J Clin Invest. 1996 Oct 1;98(7):1633–1641. doi: 10.1172/JCI118958. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marzo A. L., Lake R. A., Lo D., Sherman L., McWilliam A., Nelson D., Robinson B. W., Scott B. Tumor antigens are constitutively presented in the draining lymph nodes. J Immunol. 1999 May 15;162(10):5838–5845. [PubMed] [Google Scholar]
- Matsuda M., Salazar F., Petersson M., Masucci G., Hansson J., Pisa P., Zhang Q. J., Masucci M. G., Kiessling R. Interleukin 10 pretreatment protects target cells from tumor- and allo-specific cytotoxic T cells and downregulates HLA class I expression. J Exp Med. 1994 Dec 1;180(6):2371–2376. doi: 10.1084/jem.180.6.2371. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Medema J. P., Toes R. E., Scaffidi C., Zheng T. S., Flavell R. A., Melief C. J., Peter M. E., Offringa R., Krammer P. H. Cleavage of FLICE (caspase-8) by granzyme B during cytotoxic T lymphocyte-induced apoptosis. Eur J Immunol. 1997 Dec;27(12):3492–3498. doi: 10.1002/eji.1830271250. [DOI] [PubMed] [Google Scholar]
- Melcher A., Todryk S., Hardwick N., Ford M., Jacobson M., Vile R. G. Tumor immunogenicity is determined by the mechanism of cell death via induction of heat shock protein expression. Nat Med. 1998 May;4(5):581–587. doi: 10.1038/nm0598-581. [DOI] [PubMed] [Google Scholar]
- Morisaki T., Katano M., Ikubo A., Anan K., Nakamura M., Nakamura K., Sato H., Tanaka M., Torisu M. Immunosuppressive cytokines (IL-10, TGF-beta) genes expression in human gastric carcinoma tissues. J Surg Oncol. 1996 Dec;63(4):234–239. doi: 10.1002/(SICI)1096-9098(199612)63:4<234::AID-JSO4>3.0.CO;2-D. [DOI] [PubMed] [Google Scholar]
- Multhoff G., Botzler C., Wiesnet M., Müller E., Meier T., Wilmanns W., Issels R. D. A stress-inducible 72-kDa heat-shock protein (HSP72) is expressed on the surface of human tumor cells, but not on normal cells. Int J Cancer. 1995 Apr 10;61(2):272–279. doi: 10.1002/ijc.2910610222. [DOI] [PubMed] [Google Scholar]
- Niehans G. A., Brunner T., Frizelle S. P., Liston J. C., Salerno C. T., Knapp D. J., Green D. R., Kratzke R. A. Human lung carcinomas express Fas ligand. Cancer Res. 1997 Mar 15;57(6):1007–1012. [PubMed] [Google Scholar]
- O'Connell J., Bennett M. W., O'Sullivan G. C., Roche D., Kelly J., Collins J. K., Shanahan F. Fas ligand expression in primary colon adenocarcinomas: evidence that the Fas counterattack is a prevalent mechanism of immune evasion in human colon cancer. J Pathol. 1998 Nov;186(3):240–246. doi: 10.1002/(SICI)1096-9896(199811)186:3<240::AID-PATH173>3.0.CO;2-L. [DOI] [PubMed] [Google Scholar]
- Ochsenbein A. F., Klenerman P., Karrer U., Ludewig B., Pericin M., Hengartner H., Zinkernagel R. M. Immune surveillance against a solid tumor fails because of immunological ignorance. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2233–2238. doi: 10.1073/pnas.96.5.2233. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pena J. C., Thompson C. B., Recant W., Vokes E. E., Rudin C. M. Bcl-xL and Bcl-2 expression in squamous cell carcinoma of the head and neck. Cancer. 1999 Jan 1;85(1):164–170. doi: 10.1002/(sici)1097-0142(19990101)85:1<164::aid-cncr23>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
- Pitti R. M., Marsters S. A., Lawrence D. A., Roy M., Kischkel F. C., Dowd P., Huang A., Donahue C. J., Sherwood S. W., Baldwin D. T. Genomic amplification of a decoy receptor for Fas ligand in lung and colon cancer. Nature. 1998 Dec 17;396(6712):699–703. doi: 10.1038/25387. [DOI] [PubMed] [Google Scholar]
- Poppas D. P., Pavlovich C. P., Folkman J., Voest E. E., Chen X., Luster A. D., O'Donnell M. A. Intravesical bacille Calmette-Guérin induces the antiangiogenic chemokine interferon-inducible protein 10. Urology. 1998 Aug;52(2):268–276. [PubMed] [Google Scholar]
- Restifo N. P., Esquivel F., Kawakami Y., Yewdell J. W., Mulé J. J., Rosenberg S. A., Bennink J. R. Identification of human cancers deficient in antigen processing. J Exp Med. 1993 Feb 1;177(2):265–272. doi: 10.1084/jem.177.2.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Romero P., Dunbar P. R., Valmori D., Pittet M., Ogg G. S., Rimoldi D., Chen J. L., Liénard D., Cerottini J. C., Cerundolo V. Ex vivo staining of metastatic lymph nodes by class I major histocompatibility complex tetramers reveals high numbers of antigen-experienced tumor-specific cytolytic T lymphocytes. J Exp Med. 1998 Nov 2;188(9):1641–1650. doi: 10.1084/jem.188.9.1641. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenberg S. A. A new era for cancer immunotherapy based on the genes that encode cancer antigens. Immunity. 1999 Mar;10(3):281–287. doi: 10.1016/s1074-7613(00)80028-x. [DOI] [PubMed] [Google Scholar]
- Sahin U., Türeci O., Schmitt H., Cochlovius B., Johannes T., Schmits R., Stenner F., Luo G., Schobert I., Pfreundschuh M. Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11810–11813. doi: 10.1073/pnas.92.25.11810. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seliger B., Hohne A., Knuth A., Bernhard H., Meyer T., Tampe R., Momburg F., Huber C. Analysis of the major histocompatibility complex class I antigen presentation machinery in normal and malignant renal cells: evidence for deficiencies associated with transformation and progression. Cancer Res. 1996 Apr 15;56(8):1756–1760. [PubMed] [Google Scholar]
- Seliger B., Höhne A., Knuth A., Bernhard H., Ehring B., Tampé R., Huber C. Reduced membrane major histocompatibility complex class I density and stability in a subset of human renal cell carcinomas with low TAP and LMP expression. Clin Cancer Res. 1996 Aug;2(8):1427–1433. [PubMed] [Google Scholar]
- Seliger B., Maeurer M. J., Ferrone S. TAP off--tumors on. Immunol Today. 1997 Jun;18(6):292–299. doi: 10.1016/s0167-5699(97)01052-9. [DOI] [PubMed] [Google Scholar]
- Strand S., Hofmann W. J., Hug H., Müller M., Otto G., Strand D., Mariani S. M., Stremmel W., Krammer P. H., Galle P. R. Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells--a mechanism of immune evasion? Nat Med. 1996 Dec;2(12):1361–1366. doi: 10.1038/nm1296-1361. [DOI] [PubMed] [Google Scholar]
- Svane I. M., Engel A. M., Nielsen M. B., Ljunggren H. G., Rygaard J., Werdelin O. Chemically induced sarcomas from nude mice are more immunogenic than similar sarcomas from congenic normal mice. Eur J Immunol. 1996 Aug;26(8):1844–1850. doi: 10.1002/eji.1830260827. [DOI] [PubMed] [Google Scholar]
- Taylor-Papadimitriou J., Finn O. J. Biology, biochemistry and immunology of carcinoma-associated mucins. Immunol Today. 1997 Mar;18(3):105–107. doi: 10.1016/s0167-5699(97)01028-1. [DOI] [PubMed] [Google Scholar]
- Todryk S., Melcher A. A., Hardwick N., Linardakis E., Bateman A., Colombo M. P., Stoppacciaro A., Vile R. G. Heat shock protein 70 induced during tumor cell killing induces Th1 cytokines and targets immature dendritic cell precursors to enhance antigen uptake. J Immunol. 1999 Aug 1;163(3):1398–1408. [PubMed] [Google Scholar]
- Torzewski M., Sarbia M., Heep H., Dutkowski P., Willers R., Gabbert H. E. Expression of Bcl-X(L), an antiapoptotic member of the Bcl-2 family, in esophageal squamous cell carcinoma. Clin Cancer Res. 1998 Mar;4(3):577–583. [PubMed] [Google Scholar]
- Vánky F., Nagy N., Hising C., Sjövall K., Larson B., Klein E. Human ex vivo carcinoma cells produce transforming growth factor beta and thereby can inhibit lymphocyte functions in vitro. Cancer Immunol Immunother. 1997 Jan;43(6):317–323. doi: 10.1007/s002620050339. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wick M., Dubey P., Koeppen H., Siegel C. T., Fields P. E., Chen L., Bluestone J. A., Schreiber H. Antigenic cancer cells grow progressively in immune hosts without evidence for T cell exhaustion or systemic anergy. J Exp Med. 1997 Jul 21;186(2):229–238. doi: 10.1084/jem.186.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yannelli J. R., Hyatt C., McConnell S., Hines K., Jacknin L., Parker L., Sanders M., Rosenberg S. A. Growth of tumor-infiltrating lymphocytes from human solid cancers: summary of a 5-year experience. Int J Cancer. 1996 Feb 8;65(4):413–421. doi: 10.1002/(SICI)1097-0215(19960208)65:4<413::AID-IJC3>3.0.CO;2-#. [DOI] [PubMed] [Google Scholar]
- York I. A., Rock K. L. Antigen processing and presentation by the class I major histocompatibility complex. Annu Rev Immunol. 1996;14:369–396. doi: 10.1146/annurev.immunol.14.1.369. [DOI] [PubMed] [Google Scholar]
- Zhang K., Sikut R., Hansson G. C. A MUC1 mucin secreted from a colon carcinoma cell line inhibits target cell lysis by natural killer cells. Cell Immunol. 1997 Mar 15;176(2):158–165. doi: 10.1006/cimm.1997.1085. [DOI] [PubMed] [Google Scholar]
- van de Wiel-van Kemenade E., Ligtenberg M. J., de Boer A. J., Buijs F., Vos H. L., Melief C. J., Hilkens J., Figdor C. G. Episialin (MUC1) inhibits cytotoxic lymphocyte-target cell interaction. J Immunol. 1993 Jul 15;151(2):767–776. [PubMed] [Google Scholar]