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  • 제16권2호
  • /
  • Pages.134-139
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  • 2016
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  • 1598-2629(pISSN)
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  • 2092-6685(eISSN)
대한면역학회 (The Korean Association of Immunobiologists)
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DOI QR코드

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Enhanced Anti-tumor Reactivity of Cytotoxic T Lymphocytes Expressing PD-1 Decoy

  • Jae Hun Shin (Research Institute National Cancer Center) ;
  • Hyung Bae Park (Research Institute National Cancer Center) ;
  • Kyungho Choi (Department of Biochemistry and Molecular Biology and Department of Biomedical Sciences, Seoul National University College of Medicine)
  • 투고 : 2015.12.06
  • 심사 : 2016.03.16
  • 발행 : 2016.04.30
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초록

Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy.

키워드

과제정보

We thank Drs. Yosef Refaeli and Garry Nolan for providing us valuable materials. This work was supported by grant from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2013R1A2A2A01009444), Republic of Korea.

참고문헌

  1. Kyi, C., and M. A. Postow. 2014. Checkpoint blocking antibodies in cancer immunotherapy. FEBS Lett. 588: 368-376.
  2. Henick, B. S., R. S. Herbst, and S. B. Goldberg. 2014. The PD-1 pathway as a therapeutic target to overcome immune escape mechanisms in cancer. Expert Opin. Ther. Targets. 18: 1407-1420.
  3. Topalian, S. L., F. S. Hodi, J. R. Brahmer, S. N. Gettinger, D. C. Smith, D. F. McDermott, J. D. Powderly, R. D. Carvajal, J. A. Sosman, M. B. Atkins, P. D. Leming, D. R. Spigel, S. J. Antonia, L. Horn, C. G. Drake, D. M. Pardoll, L. Chen, W. H. Sharfman, R. A. Anders, J. M. Taube, T. L. McMiller, H. Xu, A. J. Korman, M. Jure-Kunkel, S. Agrawal, D. McDonald, G. D. Kollia, A. Gupta, J. M. Wigginton, and M. Sznol. 2012. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med. 366: 2443-2454.
  4. Topalian, S. L., M. Sznol, D. F. McDermott, H. M. Kluger, R. D. Carvajal, W. H. Sharfman, J. R. Brahmer, D. P. Lawrence, M. B. Atkins, J. D. Powderly, P. D. Leming, E. J. Lipson, I. Puzanov, D. C. Smith, J. M. Taube, J. M. Wigginton, G. D. Kollia, A. Gupta, D. M. Pardoll, J. A. Sosman, and F. S. Hodi. 2014. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J. Clin. Oncol. 32: 1020-1030.
  5. Hamid, O., C. Robert, A. Daud, F. S. Hodi, W. J. Hwu, R. Kefford, J. D. Wolchok, P. Hersey, R. W. Joseph, J. S. Weber, R. Dronca, T. C. Gangadhar, A. Patnaik, H. Zarour, A. M. Joshua, K. Gergich, J. Elassaiss-Schaap, A. Algazi, C. Mateus, P. Boasberg, P. C. Tumeh, B. Chmielowski, S. W. Ebbinghaus, X. N. Li, S. P. Kang, and A. Ribas. 2013. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N. Engl. J. Med. 369: 134-144.
  6. Philips, G. K., and M. Atkins. 2015. Therapeutic uses of anti-PD-1 and anti-PD-L1 antibodies. Int. Immunol. 27: 39-46.
  7. Okazaki, T., and T. Honjo. 2007. PD-1 and PD-1 ligands: from discovery to clinical application. Int. Immunol. 19: 813-824.
  8. Agata, Y., A. Kawasaki, H. Nishimura, Y. Ishida, T. Tsubata, H. Yagita, and T. Honjo. 1996. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int. Immunol. 8: 765-772.
  9. Dong, H., G. Zhu, K. Tamada, and L. Chen. 1999. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat. Med. 5: 1365-1369.
  10. Latchman, Y., C. R. Wood, T. Chernova, D. Chaudhary, M. Borde, I. Chernova, Y. Iwai, A. J. Long, J. A. Brown, R. Nunes, E. A. Greenfield, K. Bourque, V. A. Boussiotis, L. L. Carter, B. M. Carreno, N. Malenkovich, H. Nishimura, T. Okazaki, T. Honjo, A. H. Sharpe, and G. J. Freeman. 2001. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat. Immunol. 2: 261-268.
  11. Ishida, M., Y. Iwai, Y. Tanaka, T. Okazaki, G. J. Freeman, N. Minato, and T. Honjo. 2002. Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues. Immunol. Lett. 84: 57-62.
  12. Liang, S. C., Y. E. Latchman, J. E. Buhlmann, M. F. Tomczak, B. H. Horwitz, G. J. Freeman, and A. H. Sharpe. 2003. Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses. Eur. J. Immunol. 33: 2706-2716.
  13. Dong, H., S. E. Strome, D. R. Salomao, H. Tamura, F. Hirano, D. B. Flies, P. C. Roche, J. Lu, G. Zhu, K. Tamada, V. A. Lennon, E. Celis, and L. Chen. 2002. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat. Med. 8: 793-800.
  14. Chemnitz, J. M., R. V. Parry, K. E. Nichols, C. H. June, and J. L. Riley. 2004. SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J. Immunol. 173: 945-954.
  15. Okazaki, T., A. Maeda, H. Nishimura, T. Kurosaki, and T. Honjo. 2001. PD-1 immunoreceptor inhibits B cell receptor-mediated signaling by recruiting src homology 2-domain-containing tyrosine phosphatase 2 to phosphotyrosine. Proc. Natl. Acad. Sci. U. S. A. 98: 13866-13871.
  16. Nishimura, H., M. Nose, H. Hiai, N. Minato, and T. Honjo. 1999. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11: 141-151.
  17. Nishimura, H., T. Okazaki, Y. Tanaka, K. Nakatani, M. Hara, A. Matsumori, S. Sasayama, A. Mizoguchi, H. Hiai, N. Minato, and T. Honjo. 2001. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291: 319-322.
  18. Muenst, S., S. D. Soysal, A. Tzankov, and S. Hoeller. 2015. The PD-1/PD-L1 pathway: biological background and clinical relevance of an emerging treatment target in immunotherapy. Expert. Opin. Ther. Targets 19: 201-211.
  19. Naidoo, J., D. B. Page, B. T. Li, L. C. Connell, K. Schindler, M. E. Lacouture, M. A. Postow, and J. D. Wolchok. 2015. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann. Oncol. 26: 2375-2391.
  20. Weber, J. S., K. C. Kahler, and A. Hauschild. 2012. Management of immune-related adverse events and kinetics of response with ipilimumab. J. Clin. Oncol. 30: 2691-2697.
  21. Shin, J. H., H. B. Park, Y. M. Oh, D. P. Lim, J. E. Lee, H. H. Seo, S. J. Lee, H. S. Eom, I. H. Kim, S. H. Lee, and K. Choi. 2012. Positive conversion of negative signaling of CTLA4 potentiates antitumor efficacy of adoptive T-cell therapy in murine tumor models. Blood 119: 5678-5687.
  22. Prosser, M. E., C. E. Brown, A. F. Shami, S. J. Forman, and M. C. Jensen. 2012. Tumor PD-L1 co-stimulates primary human CD8(+) cytotoxic T cells modified to express a PD1:CD28 chimeric receptor. Mol. Immunol. 51: 263-272.