Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. Sep 1, 1996; 184(3): 1075–1082.
PMCID: PMC2192789

The Fas counterattack: Fas-mediated T cell killing by colon cancer cells expressing Fas ligand

Abstract

Tumors escape immunological rejection by a diversity of mechanisms. In this report, we demonstrate that the colon cancer cell SW620 expresses functional Fas ligand (FasL), the triggering agent of Fas receptor (FasR)-mediated apoptosis within the immune system. FasL mRNA and cell surface FasL were detected in SW620 cells using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining, respectively. We show that SW620 kills Jurkat T cells in a Fas-mediated manner. FasR-specific antisense oligonucleotide treatment, which transiently inhibited FasR expression, completely protected Jurkat cells from killing by SW620. FasL-specific antisense oligonucleotide treatment of SW620 inhibited its Jurkat-killing activity. FasL has recently been established as a mediator of immune privilege in mouse retina and testis. Our finding that colon cancer cells express functional FasL suggests it may play an analogous role in bestowing immune privilege on human tumors. HT29 and SW620 colon cancer cells were found to express FasR mRNA and cell surface FasR using RT-PCR and immunofluorescence flow cytometry, respectively. However, neither of these cells underwent apoptosis after treatment by the anti-FasR agonistic monoclonal antibody CH11. Our results therefore suggest a Fas counterattack model for immune escape in colon cancer, whereby the cancer cells resist Fas-mediated T cell cytotoxicity but express functional FasL, an apoptotic death signal to which activated T cells are inherently sensitive.

Full Text

The Full Text of this article is available as a PDF (2.7M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Broaddus RR, Wargovich MJ, Castro GA. Early stages of 1,2-dimethylhydrazine-induced colon carcinogenesis suppress immune-regulated ion transport of mouse distal colon. Cancer Res. 1994 Nov 15;54(22):5930–5936. [PubMed]
  • O'Mahony AM, O'Sullivan GC, O'Connell J, Cotter TG, Collins JK. An immune suppressive factor derived from esophageal squamous carcinoma induces apoptosis in normal and transformed cells of lymphoid lineage. J Immunol. 1993 Nov 1;151(9):4847–4856. [PubMed]
  • Yagita M, Seppo A, Renkonen O, Saksela E. Deacetylase activity of human tumor cells producing immunosuppressive aminosugars: its possible role in resistance to cell-mediated cytotoxicity. Cancer Res. 1993 Dec 1;53(23):5600–5604. [PubMed]
  • Li R, Gage D, Ladisch S. Biosynthesis and shedding of murine lymphoma gangliosides. Biochim Biophys Acta. 1993 Nov 3;1170(3):283–290. [PubMed]
  • Bergelson LD. Gangliosides and antitumor immunity. Clin Investig. 1993 Aug;71(8):590–594. [PubMed]
  • Nagata S, Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449–1456. [PubMed]
  • Yonehara S, Nishimura Y, Kishil S, Yonehara M, Takazawa K, Tamatani T, Ishii A. Involvement of apoptosis antigen Fas in clonal deletion of human thymocytes. Int Immunol. 1994 Dec;6(12):1849–1856. [PubMed]
  • Alderson MR, Tough TW, Davis-Smith T, Braddy S, Falk B, Schooley KA, Goodwin RG, Smith CA, Ramsdell F, Lynch DH. Fas ligand mediates activation-induced cell death in human T lymphocytes. J Exp Med. 1995 Jan 1;181(1):71–77. [PMC free article] [PubMed]
  • Daniel PT, Krammer PH. Activation induces sensitivity toward APO-1 (CD95)-mediated apoptosis in human B cells. J Immunol. 1994 Jun 15;152(12):5624–5632. [PubMed]
  • Ju ST, Cui H, Panka DJ, Ettinger R, Marshak-Rothstein A. Participation of target Fas protein in apoptosis pathway induced by CD4+ Th1 and CD8+ cytotoxic T cells. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4185–4189. [PMC free article] [PubMed]
  • Fisher GH, Rosenberg FJ, Straus SE, Dale JK, Middleton LA, Lin AY, Strober W, Lenardo MJ, Puck JM. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell. 1995 Jun 16;81(6):935–946. [PubMed]
  • Rieux-Laucat F, Le Deist F, Hivroz C, Roberts IA, Debatin KM, Fischer A, de Villartay JP. Mutations in Fas associated with human lymphoproliferative syndrome and autoimmunity. Science. 1995 Jun 2;268(5215):1347–1349. [PubMed]
  • Nagata S, Suda T. Fas and Fas ligand: lpr and gld mutations. Immunol Today. 1995 Jan;16(1):39–43. [PubMed]
  • Bellgrau D, Gold D, Selawry H, Moore J, Franzusoff A, Duke RC. A role for CD95 ligand in preventing graft rejection. Nature. 1995 Oct 19;377(6550):630–632. [PubMed]
  • Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science. 1995 Nov 17;270(5239):1189–1192. [PubMed]
  • Tanaka M, Suda T, Haze K, Nakamura N, Sato K, Kimura F, Motoyoshi K, Mizuki M, Tagawa S, Ohga S, et al. Fas ligand in human serum. Nat Med. 1996 Mar;2(3):317–322. [PubMed]
  • Debatin KM, Krammer PH. Resistance to APO-1 (CD95) induced apoptosis in T-ALL is determined by a BCL-2 independent anti-apoptotic program. Leukemia. 1995 May;9(5):815–820. [PubMed]
  • Shima Y, Nishimoto N, Ogata A, Fujii Y, Yoshizaki K, Kishimoto T. Myeloma cells express Fas antigen/APO-1 (CD95) but only some are sensitive to anti-Fas antibody resulting in apoptosis. Blood. 1995 Feb 1;85(3):757–764. [PubMed]
  • Owen-Schaub LB, Radinsky R, Kruzel E, Berry K, Yonehara S. Anti-Fas on nonhematopoietic tumors: levels of Fas/APO-1 and bcl-2 are not predictive of biological responsiveness. Cancer Res. 1994 Mar 15;54(6):1580–1586. [PubMed]
  • Wright SC, Zhong J, Larrick JW. Inhibition of apoptosis as a mechanism of tumor promotion. FASEB J. 1994 Jun;8(9):654–660. [PubMed]
  • Wright SC, Zhong J, Zheng H, Larrick JW. Nicotine inhibition of apoptosis suggests a role in tumor promotion. FASEB J. 1993 Aug;7(11):1045–1051. [PubMed]
  • Gibellini D, Caputo A, Celeghini C, Bassini A, La Placa M, Capitani S, Zauli G. Tat-expressing Jurkat cells show an increased resistance to different apoptotic stimuli, including acute human immunodeficiency virus-type 1 (HIV-1) infection. Br J Haematol. 1995 Jan;89(1):24–33. [PubMed]
  • Copeland KF, Haaksma AG, Goudsmit J, Krammer PH, Heeney JL. Inhibition of apoptosis in T cells expressing human T cell leukemia virus type I Tax. AIDS Res Hum Retroviruses. 1994 Oct;10(10):1259–1268. [PubMed]
  • Cascino I, Fiucci G, Papoff G, Ruberti G. Three functional soluble forms of the human apoptosis-inducing Fas molecule are produced by alternative splicing. J Immunol. 1995 Mar 15;154(6):2706–2713. [PubMed]
  • Degols G, Leonetti JP, Mechti N, Lebleu B. Antiproliferative effects of antisense oligonucleotides directed to the RNA of c-myc oncogene. Nucleic Acids Res. 1991 Feb 25;19(4):945–948. [PMC free article] [PubMed]
  • Capaccioli S, Di Pasquale G, Mini E, Mazzei T, Quattrone A. Cationic lipids improve antisense oligonucleotide uptake and prevent degradation in cultured cells and in human serum. Biochem Biophys Res Commun. 1993 Dec 15;197(2):818–825. [PubMed]
  • Matzinger P. The JAM test. A simple assay for DNA fragmentation and cell death. J Immunol Methods. 1991 Dec 15;145(1-2):185–192. [PubMed]
  • Weller M, Frei K, Groscurth P, Krammer PH, Yonekawa Y, Fontana A. Anti-Fas/APO-1 antibody-mediated apoptosis of cultured human glioma cells. Induction and modulation of sensitivity by cytokines. J Clin Invest. 1994 Sep;94(3):954–964. [PMC free article] [PubMed]
  • Owen-Schaub LB, Zhang W, Cusack JC, Angelo LS, Santee SM, Fujiwara T, Roth JA, Deisseroth AB, Zhang WW, Kruzel E, et al. Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression. Mol Cell Biol. 1995 Jun;15(6):3032–3040. [PMC free article] [PubMed]
  • Quirk SM, Cowan RG, Joshi SG, Henrikson KP. Fas antigen-mediated apoptosis in human granulosa/luteal cells. Biol Reprod. 1995 Feb;52(2):279–287. [PubMed]
  • Matsue H, Kobayashi H, Hosokawa T, Akitaya T, Ohkawara A. Keratinocytes constitutively express the Fas antigen that mediates apoptosis in IFN gamma-treated cultured keratinocytes. Arch Dermatol Res. 1995;287(3-4):315–320. [PubMed]
  • Sayama K, Yonehara S, Watanabe Y, Miki Y. Expression of Fas antigen on keratinocytes in vivo and induction of apoptosis in cultured keratinocytes. J Invest Dermatol. 1994 Sep;103(3):330–334. [PubMed]
  • Weller M, Malipiero U, Aguzzi A, Reed JC, Fontana A. Protooncogene bcl-2 gene transfer abrogates Fas/APO-1 antibody-mediated apoptosis of human malignant glioma cells and confers resistance to chemotherapeutic drugs and therapeutic irradiation. J Clin Invest. 1995 Jun;95(6):2633–2643. [PMC free article] [PubMed]
  • Itoh N, Yonehara S, Ishii A, Yonehara M, Mizushima S, Sameshima M, Hase A, Seto Y, Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. [PubMed]
  • Weller M, Malipiero U, Rensing-Ehl A, Barr PJ, Fontana A. Fas/APO-1 gene transfer for human malignant glioma. Cancer Res. 1995 Jul 1;55(13):2936–2944. [PubMed]
  • Mountz JD, Wu J, Cheng J, Zhou T. Autoimmune disease. A problem of defective apoptosis. Arthritis Rheum. 1994 Oct;37(10):1415–1420. [PubMed]
  • Cheng J, Zhou T, Liu C, Shapiro JP, Brauer MJ, Kiefer MC, Barr PJ, Mountz JD. Protection from Fas-mediated apoptosis by a soluble form of the Fas molecule. Science. 1994 Mar 25;263(5154):1759–1762. [PubMed]
  • Jättelä M, Benedict M, Tewari M, Shayman JA, Dixit VM. Bcl-x and Bcl-2 inhibit TNF and Fas-induced apoptosis and activation of phospholipase A2 in breast carcinoma cells. Oncogene. 1995 Jun 15;10(12):2297–2305. [PubMed]
  • Itoh N, Tsujimoto Y, Nagata S. Effect of bcl-2 on Fas antigen-mediated cell death. J Immunol. 1993 Jul 15;151(2):621–627. [PubMed]
  • Yoshino T, Kondo E, Cao L, Takahashi K, Hayashi K, Nomura S, Akagi T. Inverse expression of bcl-2 protein and Fas antigen in lymphoblasts in peripheral lymph nodes and activated peripheral blood T and B lymphocytes. Blood. 1994 Apr 1;83(7):1856–1861. [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...