Asian Pacific Journal of Cancer Prevention

  • 제15권13호
  • /
  • Pages.5181-5186
  • /
  • 2014
  • /
  • 1513-7368(pISSN)
  • /
  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
권호 표지
DOI QR코드

DOI QR Code

Tumor-Derived Transforming Growth Factor-β is Critical for Tumor Progression and Evasion from Immune Surveillance

  • Li, Zheng (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Zhang, Li-Juan (Tianjin Medical University) ;
  • Zhang, Hong-Ru (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Tian, Gao-Fei (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Tian, Jun (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Mao, Xiao-Li (Department of Immunology, School of Basic Medical Science, Wuhan University) ;
  • Jia, Zheng-Hu (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Meng, Zi-Yu (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Zhao, Li-Qing (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Yin, Zhi-Nan (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University) ;
  • Wu, Zhen-Zhou (State Key Laboratory of Medical Chemical Biology, College of Life Sciences, Nankai University)
  • 발행 : 2014.07.15
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.

키워드

참고문헌

  1. Akhurst RJ, Derynck R (2001). TGF-beta signaling in cancer--a double-edged sword. Trends Cell Biol, 11, 44-51.
  2. Bierie B, Moses HL (2006). Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer, 6, 506-20. https://doi.org/10.1038/nrc1926
  3. Buck MB, Fritz P, Dippon J, et al (2004). Prognostic significance of transforming growth factor beta receptor II in estrogen receptor-negative breast cancer patients. Clin Cancer Res, 10, 491-8. https://doi.org/10.1158/1078-0432.CCR-0320-03
  4. Centuori SM, Trad M, LaCasse CJ, et al (2012). Myeloid-derived suppressor cells from tumor-bearing mice impair TGF-beta-induced differentiation of $CD4^{+}CD25^{+}FoxP3^{+}$ Tregs from $CD4^{+}CD25^{-}FoxP3-$ T cells. J Leukoc Biol, 92, 987-97. https://doi.org/10.1189/jlb.0911465
  5. Chen W, Jin W, Hardegen N, et al (2003). Conversion of peripheral $CD4^{+}CD25^{-}$ naive T cells to $CD4^{+}CD25^{+}$ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med, 198, 1875-86. https://doi.org/10.1084/jem.20030152
  6. Chung DJ, Rossi M, Romano E, et al (2009). Indoleamine 2, 3-dioxygenase-expressing mature human monocyte-derived dendritic cells expand potent autologous regulatory T cells. Blood, 114, 555-63. https://doi.org/10.1182/blood-2008-11-191197
  7. Curiel TJ, Coukos G, Zou L, et al (2004). Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med, 10, 942-9. https://doi.org/10.1038/nm1093
  8. Donkor MK, Sarkar A, Li MO (2012). Tgf-beta1 produced by activated $CD4 (^{+})$ T cells antagonizes T cell surveillance of tumor development. Oncoimmunology, 1, 162-71. https://doi.org/10.4161/onci.1.2.18481
  9. Ghiringhelli F, Puig PE, Roux S, et al (2005). Tumor cells convert immature myeloid dendritic cells into TGF-beta-secreting cells inducing $CD4^{+}CD25^{+}$ regulatory T cell proliferation. J Exp Med, 202, 919-29. https://doi.org/10.1084/jem.20050463
  10. Gorelik L, Flavell RA (2001). Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells. Nat Med, 7, 1118-22. https://doi.org/10.1038/nm1001-1118
  11. Hu JL, Yang Z, Tang JR, et al (2013). Effects of gastric cancer cells on the differentiation of Treg cells. Asian Pac J Cancer Prev, 14, 4607-10. https://doi.org/10.7314/APJCP.2013.14.8.4607
  12. Jerant AF, Johnson JT, Sheridan CD, Caffrey TJ (2000). Early detection and treatment of skin cancer. Am Fam Physician, 62, 357-68, 75-6, 81-2.
  13. Kulkarni AB, Huh CG, Becker D, et al (1993). Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci U S A, 90, 770-4. https://doi.org/10.1073/pnas.90.2.770
  14. Li MO, Flavell RA (2008). TGF-beta: a master of all T cell trades. Cell, 134, 392-404. https://doi.org/10.1016/j.cell.2008.07.025
  15. Li Z, Chen L, Rubinstein MP (2013). Cancer immunotherapy: are we there yet? Exp Hematol Oncol, 2, 33. https://doi.org/10.1186/2162-3619-2-33
  16. Liu CY, Wang YM, Wang CL, et al (2010). Population alterations of L-arginase- and inducible nitric oxide synthase-expressed $CD11b^{+}/CD14 (-)/CD15^{+}/CD33^{+}$ myeloid-derived suppressor cells and $CD8^{+}$ T lymphocytes in patients with advanced-stage non-small cell lung cancer. J Cancer Res Clin Oncol, 136, 35-45. https://doi.org/10.1007/s00432-009-0634-0
  17. Marigo I, Dolcetti L, Serafini P, et al (2008). Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunol Rev, 222, 162-79. https://doi.org/10.1111/j.1600-065X.2008.00602.x
  18. Massague J (2008). TGFbeta in Cancer. Cell, 134, 215-30. https://doi.org/10.1016/j.cell.2008.07.001
  19. McKarns SC, Schwartz RH, Kaminski NE (2004). Smad3 is essential for TGF-beta 1 to suppress IL-2 production and TCR-induced proliferation, but not IL-2-induced proliferation. J Immunol, 172, 4275-84. https://doi.org/10.4049/jimmunol.172.7.4275
  20. Siegel PM, Massague J (2003). Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer, 3, 807-21. https://doi.org/10.1038/nrc1208
  21. Thomas DA, Massague J (2005). TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell, 8, 369-80. https://doi.org/10.1016/j.ccr.2005.10.012
  22. Tripsianis G, Papadopoulou E, Romanidis K (2013). Overall survival and clinicopathological characteristics of patients with breast cancer in relation to the expression pattern of HER-2, IL-6, TNF-alpha and TGF-beta1. Asian Pac J Cancer Prev, 14, 6813-20. https://doi.org/10.7314/APJCP.2013.14.11.6813
  23. Willimsky G, Blankenstein T (2005). Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance. Nature, 437, 141-6. https://doi.org/10.1038/nature03954
  24. Yamazaki S, Iyoda T, Tarbell K, et al (2003). Direct expansion of functional $CD25^{+} CD4^{+}$ regulatory T cells by antigen-processing dendritic cells. J Exp Med, 198, 235-47. https://doi.org/10.1084/jem.20030422
  25. Yang L, Huang J, Ren X, et al (2008). Abrogation of TGF beta signaling in mammary carcinomas recruits $Gr-1^{+}CD11b^{+}$ myeloid cells that promote metastasis. Cancer Cell, 13, 23-35. https://doi.org/10.1016/j.ccr.2007.12.004
  26. Zou W (2006). Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol, 6, 295-307. https://doi.org/10.1038/nri1806

피인용 문헌

  1. Inhibition Effects of Lamellarin D on Human Leukemia K562 Cell Proliferation and Underlying Mechanisms vol.15, pp.22, 2014, https://doi.org/10.7314/APJCP.2014.15.22.9915
  2. New Therapeutic Schedule for Prostatic Cancer-3 Cells with ET-1 RNAi and Endostar vol.15, pp.23, 2015, https://doi.org/10.7314/APJCP.2014.15.23.10079
  3. The Dynamics of Interactions Among Immune and Glioblastoma Cells vol.17, pp.4, 2015, https://doi.org/10.1007/s12017-015-8362-x
  4. TGF-β induces HLA-G expression through inhibiting miR-152 in gastric cancer cells vol.22, pp.1, 2015, https://doi.org/10.1186/s12929-015-0177-4
  5. Augmented anti-tumor activity of NK-92 cells expressing chimeric receptors of TGF-βR II and NKG2D vol.66, pp.4, 2017, https://doi.org/10.1007/s00262-017-1959-1
  6. Role of Natural Killer Cells in HIV-Associated Malignancies vol.8, pp.1664-3224, 2017, https://doi.org/10.3389/fimmu.2017.00315
  7. Critical Role of Myeloid-Derived Suppressor Cells in Tumor-Induced Liver Immune Suppression through Inhibition of NKT Cell Function vol.8, pp.1664-3224, 2017, https://doi.org/10.3389/fimmu.2017.00129
  8. Short hairpin RNA silencing of TGF-βRII and FZD-7 synergistically suppresses proliferation and metastasis of hepatocellular carcinoma cells vol.11, pp.3, 2016, https://doi.org/10.3892/ol.2016.4208
  9. The role of the immune system in neurofibromatosis type 1-associated nervous system tumors vol.6, pp.1, 2017, https://doi.org/10.2217/cns-2016-0024