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Immunotherapy of Cancer pp 103–118Cite as

Gene Therapy to Improve Migration of T Cells to the Tumor Site

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 651))

Abstract

One requirement for anti-tumor T cells to be effective is their successful traffic to tumor sites. Trafficking of T cells to lymphoid organs and peripheral tissues is a multistage process. Soluble and tissue-bonded chemokines interacting with chemokine receptors expressed by T lymphocytes certainly play a pivotal role in determining migration under physiologic conditions and during inflammation. Therefore a match between the chemokines the tumor produces and the chemokine receptors the effector T cells express is required. Since chemokine produced by the targeted tumor may not match the subset of chemokine receptors expressed by T cells, gene therapy can be used to force the expression of the specific chemokine receptor by effector T cells so that the anti-tumor activity of adoptively transferred anti-tumor T cells is maximized.

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References

  1. Mackay, C. R. (2001) Chemokines: Immunology’s high impact factors. Nat Immunol 2, 95–101.

    Article  PubMed  CAS  Google Scholar 

  2. Mantovani, A., Allavena, P., Sozzani, S., Vecchi, A., Locati, M., and Sica, A. (2004) Chemokines in the recruitment and shaping of the leukocyte infiltrate of tumors. Semin Cancer Biol 14, 155–160.

    Article  PubMed  CAS  Google Scholar 

  3. Balkwill, F. (2004) Cancer and the chemokine network. Nat Rev Cancer 4, 540–550.

    Article  PubMed  CAS  Google Scholar 

  4. Sackstein, R. (2005) The lymphocyte homing receptors: gatekeepers of the multistep paradigm. Curr Opin Hematol 12, 444–450.

    Article  PubMed  Google Scholar 

  5. Liotta, L. A. and Kohn, E. C. (2001) The microenvironment of the tumour-host interface. Nature 411, 375–379.

    Article  PubMed  CAS  Google Scholar 

  6. Dunn, G. P., Old, L. J., and Schreiber, R. D. (2004) The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21, 137–148.

    Article  PubMed  CAS  Google Scholar 

  7. Vicari, A. P. and Caux, C. (2002) Chemokines in cancer. Cytokine Growth Factor Rev 13, 143–154.

    Article  PubMed  CAS  Google Scholar 

  8. Moran, C. J., Arenberg, D. A., Huang, C. C., Giordano, T. J., Thomas, D. G., Misek, D. E., Chen, G., Iannettoni, M. D., Orringer, M. B., Hanash, S., and Beer, D. G. (2002) RANTES expression is a predictor of survival in stage I lung adenocarcinoma. Clin Cancer Res 8, 3803–3812.

    PubMed  CAS  Google Scholar 

  9. Tang, K. F., Tan, S. Y., Chan, S. H., Chong, S. M., Loh, K. S., Tan, L. K., and Hu, H. (2001) A distinct expression of CC chemokines by macrophages in nasopharyngeal carcinoma: implication for the intense tumor infiltration by T lymphocytes and macrophages. Hum Pathol 32, 42–49.

    Article  PubMed  CAS  Google Scholar 

  10. Negus, R. P., Stamp, G. W., Hadley, J., and Balkwill, F. R. (1997) Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines. Am J Pathol 150, 1723–1734.

    PubMed  CAS  Google Scholar 

  11. Monti, P., Leone, B. E., Marchesi, F., Balzano, G., Zerbi, A., Scaltrini, F., Pasquali, C., Calori, G., Pessi, F., Sperti, C., Di, C. V, Allavena, P., and Piemonti, L. (2003) The CC chemokine MCP-1/CCL2 in pancreatic cancer progression: regulation of expression and potential mechanisms of antimalignant activity. Cancer Res 63, 7451–7461.

    PubMed  CAS  Google Scholar 

  12. Gabrilovich, D. (2004) Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nat Rev Immunol 4, 941–952.

    Article  PubMed  CAS  Google Scholar 

  13. Elgert, K. D., Alleva, D. G., and Mullins, D. W. (1998) Tumor-induced immune dysfunction: the macrophage connection. J Leukoc Biol 64, 275–290.

    PubMed  CAS  Google Scholar 

  14. Mantovani, A., Sozzani, S., Locati, M., Allavena, P., and Sica, A. (2002) Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23, 549–555.

    Article  PubMed  CAS  Google Scholar 

  15. Adema, G. J., Hartgers, F., Verstraten, R., de, V. E., Marland, G., Menon, S., Foster, J., Xu, Y., Nooyen, P., McClanahan, T., Bacon, K. B., and Figdor, C. G. (1997) A dendritic-cell-derived C-C chemokine that preferentially attracts naive T cells. Nature 387, 713–717.

    Article  PubMed  CAS  Google Scholar 

  16. Balkwill, F. (2004) Cancer and the chemokine network. Nat Rev Cancer 4, 540–550.

    Article  PubMed  CAS  Google Scholar 

  17. van den, B. A., Visser, L., and Poppema, S. (1999) High expression of the CC chemokine TARC in Reed-Sternberg cells. A possible explanation for the characteristic T-cell infiltratein Hodgkin's lymphoma. Am J Pathol 154, 1685–1691.

    Article  Google Scholar 

  18. Maggio, E. M., van den, B. A., Visser, L., Diepstra, A., Kluiver, J., Emmens, R., and Poppema, S. (2002) Common and differential chemokine expression patterns in rs cells of NLP, EBV positive and negative classical Hodgkin lymphomas. Int J Cancer 99, 665–672.

    Article  PubMed  CAS  Google Scholar 

  19. Ishida, T., Ishii, T., Inagaki, A., Yano, H., Komatsu, H., Iida, S., Inagaki, H., and Ueda, R. (2006) Specific recruitment of CC chemokine receptor 4-positive regulatory T cells in Hodgkin lymphoma fosters immune privilege. Cancer Res 66, 5716–5722.

    Article  PubMed  CAS  Google Scholar 

  20. Iellem, A., Mariani, M., Lang, R., Recalde, H., Panina-Bordignon, P., Sinigaglia, F., and D’Ambrosio, D. (2001) Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells. J Exp Med 194, 847–853.

    Article  PubMed  CAS  Google Scholar 

  21. D'Ambrosio, D., Iellem, A., Bonecchi, R., Mazzeo, D., Sozzani, S., Mantovani, A., and Sinigaglia, F. (1998) Selective up-regulation of chemokine receptors CCR4 and CCR8 upon activation of polarized human type 2 Th cells. J Immunol 161, 5111–5115.

    PubMed  Google Scholar 

  22. Marshall, N. A., Christie, L. E., Munro, L. R., Culligan, D. J., Johnston, P. W., Barker, R. N., and Vickers, M. A. (2004) Immunosuppressive regulatory T cells are abundant in the reactive lymphocytes of Hodgkin lymphoma. Blood 103, 1755–1762.

    Article  PubMed  CAS  Google Scholar 

  23. Curiel, T. J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., Evdemon-Hogan, M., Conejo-Garcia, J. R., Zhang, L., Burow, M., Zhu, Y., Wei, S., Kryczek, I., Daniel, B., Gordon, A., Myers, L., Lackner, A., Disis, M. L., Knutson, K. L., Chen, L., and Zou, W. (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10, 942–949.

    Article  PubMed  CAS  Google Scholar 

  24. Wilkinson, P. C. (1998) Assays of leukocyte locomotion and chemotaxis. J Immunol Methods 216, 139–153.

    Article  PubMed  CAS  Google Scholar 

  25. Capsoni, F., Minonzio, F., Ongari, A. M., and Zanussi, C. (1989) A new simplified single-filter assay for 'in vitro' evaluation of chemotaxis of 51Cr-labeled polymorphonuclear leukocytes. J Immunol Methods 120, 125–131.

    Article  PubMed  CAS  Google Scholar 

  26. Wilkinson, P. C. (1998) Assays of leukocyte locomotion and chemotaxis. J Immunol Methods 216, 139–153.

    Article  PubMed  CAS  Google Scholar 

  27. Horwitz, D. A. and Garrett, M. A. (1971) Use of leukocyte chemotaxis in vitro to assay mediators generated by immune reactions. I. Quantitation of mononuclear and polymorphonuclear leukocyte chemotaxis with polycarbonate (nuclepore) filters. J Immunol 106, 649–655.

    PubMed  CAS  Google Scholar 

  28. Falk, W., Goodwin, R. H., Jr., and Leonard, E. J. (1980) A 48-well micro chemotaxis assembly for rapid and accurate measurement of leukocyte migration, J Immunol Methods 33, 239–247.

    PubMed  CAS  Google Scholar 

  29. Roth, S. J., Carr, M. W., Rose, S. S., and Springer, T. A. (1995) Characterization of transendothelial chemotaxis of T lymphocytes. J Immunol Methods 188, 97–116.

    Article  PubMed  CAS  Google Scholar 

  30. De Clerck, L. S., Bridts, C. H., Mertens, A. M., Moens, M. M., and Stevens, W. J. (1994) Use of fluorescent dyes in the determination of adherence of human leucocytes to endothelial cells and the effect of fluorochromes on cellular function. J Immunol Methods 172, 115–124.

    Article  PubMed  Google Scholar 

  31. Frevert, C. W., Wong, V. A., Goodman, R. B., Goodwin, R., and Martin, T. R. (1998) Rapid fluorescence-based measurement of neutrophil migration in vitro. J Immunol Methods 213, 41–52.

    Article  PubMed  CAS  Google Scholar 

  32. Butt, O. I., Krishnan, P., Kulkarni, S. S., Moldovan, L., and Moldovan, N. I. (2005) Quantification and functional analysis of chemotaxis by laser scanning cytometry. Cytometry A 64, 10–15.

    PubMed  Google Scholar 

  33. Molema, G., Mesander, G., Kroesen, B. J., Helfrich, W., Meijer, D. K., and de Leij, L. F. (1998) Analysis of in vitro lymphocyte adhesion and transendothelial migration by fluorescent-beads-based flow cytometric cell counting. Cytometry 32, 37–43.

    Article  PubMed  CAS  Google Scholar 

  34. Vishwanath, R. P., Brown, C. E., Wagner, J. R., Meechoovet, H. B., Naranjo, A., Wright, C. L., Olivares, S., Qian, D., Cooper, L. J., and Jensen, M. C. (2005) A quantitative high-throughput chemotaxis assay using bioluminescent reporter cells. J Immunol. Methods 302, 78–89.

    Article  PubMed  CAS  Google Scholar 

  35. Lyons, A. B. (2000) Analysing cell division in vivo and in vitro using flow cytometric measurement of CFSE dye dilution. J Immunol Methods 243, 147–154.

    Article  PubMed  CAS  Google Scholar 

  36. Mandl, S., Schimmelpfennig, C., Edinger, M., Negrin, R. S., and Contag, C. H. (2002) Understanding immune cell trafficking patterns via in vivo bioluminescence imaging. J Cell Biochem. Suppl 39, 239–248.

    Article  PubMed  Google Scholar 

  37. Okabe, M., Ikawa, M., Kominami, K., Nakanishi, T., and Nishimune, Y. (1997) ‘Green mice’ as a source of ubiquitous green cells. FEBS Lett 407, 313–319.

    Article  PubMed  CAS  Google Scholar 

  38. Edinger, M., Hoffmann, P., Contag, C. H., and Negrin, R. S. (2003) Evaluation of effector cell fate and function by in vivo bioluminescence imaging. Methods 31, 172–179.

    Article  PubMed  CAS  Google Scholar 

  39. Bhaumik, S. and Gambhir, S. S. (2002) Optical imaging of Renilla luciferase reporter gene expression in living mice. Proc Natl Acad Sci. US A 99, 377–382.

    Article  CAS  Google Scholar 

  40. Greer, L. F., III and Szalay, A. A. (2002) Imaging of light emission from the expression of luciferases in living cells and organisms: A review. Luminescence 17, 43–74.

    Article  PubMed  CAS  Google Scholar 

  41. Rabinovich, B. A., Ye, Y., Etto, T., Chen, J. Q., Levitsky, H. I., Overwijk, W. W., Cooper, L. J., Gelovani, J., and Hwu, P. (2008) Visualizing fewer than 10 mouse T cells with an enhanced firefly luciferase in immunocompetent mouse models of cancer. Proc Natl Acad Sci USA 105, 14342–14346.

    Article  PubMed  CAS  Google Scholar 

  42. Di Stasi, A., De Angelis, B., Rooney, C. M., Zhang, L., Mahendravada, A., Foster, A. E., Heslop, H. E., Brenner, M. K., Dotti, G., and Savoldo, B. (2009) T lymphocytes coexpressing CCR4 and a chimeric antigen receptor targeting CD30 have improved homing and antitumor activity in a Hodgkin tumor model. Blood 113, 6392–6402.

    Google Scholar 

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Author information

Authors and Affiliations

  1. Center for Cell and Gene Therapy, Department of Pediatrics, Baylor College of Medicine, The Methodist Hospital and Texas Children’s Hospital, Houston, TX, USA

    Barbara Savoldo

Authors
  1. Antonio Di Stasi
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  2. Biagio De Angelis
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  3. Barbara Savoldo
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Editors and Affiliations

  1. , Center for Cell and Gene Therapy, Baylor College of Medicine, Baylor Plaza One, Houston, 77030, USA

    Patricia Yotnda

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Di Stasi, A., De Angelis, B., Savoldo, B. (2010). Gene Therapy to Improve Migration of T Cells to the Tumor Site. In: Yotnda, P. (eds) Immunotherapy of Cancer. Methods in Molecular Biology, vol 651. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-786-0_7

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  • DOI: https://doi.org/10.1007/978-1-60761-786-0_7

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-785-3

  • Online ISBN: 978-1-60761-786-0

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