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. 1998 Mar;93(3):390–397. doi: 10.1046/j.1365-2567.1998.00450.x

Gene transfer of costimulatory molecules into a human colorectal cancer cell line: requirement of CD54, CD80 and class II MHC expression for enhanced immunogenicity.

M Lindauer 1, W Rudy 1, B Gückel 1, M V Doeberitz 1, S C Meuer 1, U Moebius 1
PMCID: PMC1364088  PMID: 9640250

Abstract

Colorectal cancer is considered a non-immunogenic malignany. One strategy to augment the immunogenicity of such tumours is represented by the expression of costimulatory molecules by gene transfer. Using transfected variants of the human colorectal cancer cell line SW480 we tested various costimulatory molecules (CD80, CD86, CD54) and a class II major histocompatibility complex (MHC) allele (HLA-DR3) alone or in combination on their ability to support primary T-lymphocyte activation in vitro. Expression of CD80 or CD86 similarly as the combination of both was not sufficient to induce proliferation of human allogeneic T cells. Expression of CD54 together with CD80 strongly augmented the costimulatory function of CD80, as observed in the presence of a CD3 monoclonal antibody (mAb), but did not lead directly to a T-cell response against modified tumour cells. Importantly, SW480 cells coexpressing CD54, CD80 and the HLA-DR3 allele effectively promoted T-lymphocyte proliferation. Moreover, the use of such CD54+/CD80+/HLA-DR3+ SW480 variants for repetitive stimulations resulted in the generation of T-cell lines predominantly composed of CD8+ T cells exhibiting class I MHC restricted cytolytic activity towards untransfected SW480 tumour cells. This demonstrates that the generation of immunogenic tumour cell variants, i.e. for the use as cellular vaccines, requires multiple genetic alterations in the case of non-immunogenic human tumours cells, such as colorectal cancer cells.

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Selected References

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  1. Altmann D. M., Hogg N., Trowsdale J., Wilkinson D. Cotransfection of ICAM-1 and HLA-DR reconstitutes human antigen-presenting cell function in mouse L cells. Nature. 1989 Apr 6;338(6215):512–514. doi: 10.1038/338512a0. [DOI] [PubMed] [Google Scholar]
  2. Baskar S., Glimcher L., Nabavi N., Jones R. T., Ostrand-Rosenberg S. Major histocompatibility complex class II+B7-1+ tumor cells are potent vaccines for stimulating tumor rejection in tumor-bearing mice. J Exp Med. 1995 Feb 1;181(2):619–629. doi: 10.1084/jem.181.2.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boussiotis V. A., Freeman G. J., Gray G., Gribben J., Nadler L. M. B7 but not intercellular adhesion molecule-1 costimulation prevents the induction of human alloantigen-specific tolerance. J Exp Med. 1993 Nov 1;178(5):1753–1763. doi: 10.1084/jem.178.5.1753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chen L., Ashe S., Brady W. A., Hellström I., Hellström K. E., Ledbetter J. A., McGowan P., Linsley P. S. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell. 1992 Dec 24;71(7):1093–1102. doi: 10.1016/s0092-8674(05)80059-5. [DOI] [PubMed] [Google Scholar]
  5. Chen L., McGowan P., Ashe S., Johnston J., Li Y., Hellström I., Hellström K. E. Tumor immunogenicity determines the effect of B7 costimulation on T cell-mediated tumor immunity. J Exp Med. 1994 Feb 1;179(2):523–532. doi: 10.1084/jem.179.2.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Damle N. K., Klussman K., Leytze G., Myrdal S., Aruffo A., Ledbetter J. A., Linsley P. S. Costimulation of T lymphocytes with integrin ligands intercellular adhesion molecule-1 or vascular cell adhesion molecule-1 induces functional expression of CTLA-4, a second receptor for B7. J Immunol. 1994 Mar 15;152(6):2686–2697. [PubMed] [Google Scholar]
  7. Damle N. K., Klussman K., Linsley P. S., Aruffo A. Differential costimulatory effects of adhesion molecules B7, ICAM-1, LFA-3, and VCAM-1 on resting and antigen-primed CD4+ T lymphocytes. J Immunol. 1992 Apr 1;148(7):1985–1992. [PubMed] [Google Scholar]
  8. Damle N. K., Klussman K., Linsley P. S., Aruffo A., Ledbetter J. A. Differential regulatory effects of intercellular adhesion molecule-1 on costimulation by the CD28 counter-receptor B7. J Immunol. 1992 Oct 15;149(8):2541–2548. [PubMed] [Google Scholar]
  9. Döhring C., Angman L., Spagnoli G., Lanzavecchia A. T-helper- and accessory-cell-independent cytotoxic responses to human tumor cells transfected with a B7 retroviral vector. Int J Cancer. 1994 Jun 1;57(5):754–759. doi: 10.1002/ijc.2910570524. [DOI] [PubMed] [Google Scholar]
  10. Freeman G. J., Freedman A. S., Segil J. M., Lee G., Whitman J. F., Nadler L. M. B7, a new member of the Ig superfamily with unique expression on activated and neoplastic B cells. J Immunol. 1989 Oct 15;143(8):2714–2722. [PubMed] [Google Scholar]
  11. Freeman G. J., Gribben J. G., Boussiotis V. A., Ng J. W., Restivo V. A., Jr, Lombard L. A., Gray G. S., Nadler L. M. Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation. Science. 1993 Nov 5;262(5135):909–911. doi: 10.1126/science.7694363. [DOI] [PubMed] [Google Scholar]
  12. Gimmi C. D., Freeman G. J., Gribben J. G., Gray G., Nadler L. M. Human T-cell clonal anergy is induced by antigen presentation in the absence of B7 costimulation. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6586–6590. doi: 10.1073/pnas.90.14.6586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gimmi C. D., Freeman G. J., Gribben J. G., Sugita K., Freedman A. S., Morimoto C., Nadler L. M. B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2. Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6575–6579. doi: 10.1073/pnas.88.15.6575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gückel B., Lindauer M., Rudy W., Habicht A., Siebels M., Kaul S., Bastert G., Meuer S. C., Moebius U. CD80-transfected human breast and ovarian tumor cell lines: improved immunogenicity and induction of cytolytic CD8+ T lymphocytes. Cytokines Mol Ther. 1995 Sep;1(3):211–221. [PubMed] [Google Scholar]
  15. Habicht A., Lindauer M., Galmbacher P., Rudy W., Gebert J., Schackert H. K., Meuer S. C., Moebius U. Development of immunogenic colorectal cancer cell lines for vaccination: expression of CD80 (B7.1) is not sufficient to restore impaired primary T cell activation in vitro. Eur J Cancer. 1995 Dec;31A(13-14):2396–2402. doi: 10.1016/0959-8049(95)00435-1. [DOI] [PubMed] [Google Scholar]
  16. Hathcock K. S., Laszlo G., Dickler H. B., Bradshaw J., Linsley P., Hodes R. J. Identification of an alternative CTLA-4 ligand costimulatory for T cell activation. Science. 1993 Nov 5;262(5135):905–907. doi: 10.1126/science.7694361. [DOI] [PubMed] [Google Scholar]
  17. Hodge J. W., Abrams S., Schlom J., Kantor J. A. Induction of antitumor immunity by recombinant vaccinia viruses expressing B7-1 or B7-2 costimulatory molecules. Cancer Res. 1994 Nov 1;54(21):5552–5555. [PubMed] [Google Scholar]
  18. Janeway C. A., Jr, Bottomly K. Signals and signs for lymphocyte responses. Cell. 1994 Jan 28;76(2):275–285. doi: 10.1016/0092-8674(94)90335-2. [DOI] [PubMed] [Google Scholar]
  19. Li Y., McGowan P., Hellström I., Hellström K. E., Chen L. Costimulation of tumor-reactive CD4+ and CD8+ T lymphocytes by B7, a natural ligand for CD28, can be used to treat established mouse melanoma. J Immunol. 1994 Jul 1;153(1):421–428. [PubMed] [Google Scholar]
  20. Linsley P. S., Ledbetter J. A. The role of the CD28 receptor during T cell responses to antigen. Annu Rev Immunol. 1993;11:191–212. doi: 10.1146/annurev.iy.11.040193.001203. [DOI] [PubMed] [Google Scholar]
  21. Meuer S. C., Hussey R. E., Fabbi M., Fox D., Acuto O., Fitzgerald K. A., Hodgdon J. C., Protentis J. P., Schlossman S. F., Reinherz E. L. An alternative pathway of T-cell activation: a functional role for the 50 kd T11 sheep erythrocyte receptor protein. Cell. 1984 Apr;36(4):897–906. doi: 10.1016/0092-8674(84)90039-4. [DOI] [PubMed] [Google Scholar]
  22. Norton S. D., Zuckerman L., Urdahl K. B., Shefner R., Miller J., Jenkins M. K. The CD28 ligand, B7, enhances IL-2 production by providing a costimulatory signal to T cells. J Immunol. 1992 Sep 1;149(5):1556–1561. [PubMed] [Google Scholar]
  23. Rudy W., Gückel B., Siebels M., Lindauer M., Meuer S. C., Moebius U. Differential function of CD80- and CD86-transfected human melanoma cells in the presence of IL-12 and IFN-gamma. Int Immunol. 1997 Jun;9(6):853–860. doi: 10.1093/intimm/9.6.853. [DOI] [PubMed] [Google Scholar]
  24. Stevens E. J., Jacknin L., Robbins P. F., Kawakami Y., el Gamil M., Rosenberg S. A., Yannelli J. R. Generation of tumor-specific CTLs from melanoma patients by using peripheral blood stimulated with allogeneic melanoma tumor cell lines. Fine specificity and MART-1 melanoma antigen recognition. J Immunol. 1995 Jan 15;154(2):762–771. [PubMed] [Google Scholar]
  25. Townsend S. E., Allison J. P. Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells. Science. 1993 Jan 15;259(5093):368–370. doi: 10.1126/science.7678351. [DOI] [PubMed] [Google Scholar]
  26. Walunas T. L., Bakker C. Y., Bluestone J. A. CTLA-4 ligation blocks CD28-dependent T cell activation. J Exp Med. 1996 Jun 1;183(6):2541–2550. doi: 10.1084/jem.183.6.2541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. van Noesel C., Miedema F., Brouwer M., de Rie M. A., Aarden L. A., van Lier R. A. Regulatory properties of LFA-1 alpha and beta chains in human T-lymphocyte activation. Nature. 1988 Jun 30;333(6176):850–852. doi: 10.1038/333850a0. [DOI] [PubMed] [Google Scholar]
  28. van Seventer G. A., Newman W., Shimizu Y., Nutman T. B., Tanaka Y., Horgan K. J., Gopal T. V., Ennis E., O'Sullivan D., Grey H. Analysis of T cell stimulation by superantigen plus major histocompatibility complex class II molecules or by CD3 monoclonal antibody: costimulation by purified adhesion ligands VCAM-1, ICAM-1, but not ELAM-1. J Exp Med. 1991 Oct 1;174(4):901–913. doi: 10.1084/jem.174.4.901. [DOI] [PMC free article] [PubMed] [Google Scholar]

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