Citation: | XU Weili, YYANG Xiaofeng, LI Meng, ZHOU Hui, LI Suolin. yeloid-derived Suppressor Cells Inhibit Proliferation and Killing Activity of Neuroblastoma Antigen-specific Cytotoxic T Lymphocyte in vitro[J]. Cancer Research on Prevention and Treatment, 2017, 44(11): 728-732. DOI: 10.3971/j.issn.1000-8578.2017.17.0709 |
To explore the inhibitory role of myeloid-derived suppressor cell (MDSC) in the proliferation and killing activity of neuroblastoma antigen-specific cytotoxic T lymphocyte (CTL) in vitro.
The neuroblastoma antigen specific CTLs were successfully prepared on the basis of cultivation of neuroblastoma SK-N-SH cells and separation of BALB/c mice myeloid-derived dendritic cell (DC) and CD3+T cells in vitro. MDSCs were purified and cultivated with CTLs, then the inhibitory role of MDSC in the proliferation of CTL was detected by fluorescence staining of 5, 6-carboxyfluorescein diacetate succinimidyl ester (CFSE) and flow cytometry. Furthermore, CTL, SK-N-SH and MDSC were mixed and cultivated, the killing rate of CTL on SK-N-SH and the secretion of IL-2, IFN-γ in supernatant of the different groups were detected by ELISA.
After magnetic cell sorting, the rate of Gr-1+CD11b+MDSC reached to 84.6% by flow cytometry test. The levels of IL-2 and IFN-γ in supernatant of antigen-loaded CTLs were significantly higher than those in supernatant of T cells (P < 0.05). The proliferation of CTLs cultivated with MDSC was significantly inhibited, with strong fluorescence in view: however, CTLs cultivated alone proliferated obviously, with weak fluorescence intensity. The killing rate of CTLs to SK-N-SH in MDSC+CTL+SK-N-SH group was significant lower than that in CTL+SK-N-SH group (t=6.506, P < 0.001). Significant difference existed in the secretion levels of IL-2 and IFN-γ in the supernatant between the two groups (all P < 0.01).
MDSC inhibite the proliferation and activity of neuroblastoma antigen-specific CTLs in vitro result in immune tolerance and reduced the killing effect of CTL on neuroblastoma cells.
[1] |
侯渊涛, 刘璐, 王常林.神经母细胞瘤的免疫学治疗进展[J].临床小儿外科杂志, 2011, 10(4): 290-3. http://d.wanfangdata.com.cn/Periodical/lcxewkzz201104020
Hou YT, Liu L, Wang CL. Advances in immunotherapy of neuroblastoma[J]. Lin Chuang Xiao Er Wai Ke Za Zhi, 2011, 10(4): 290-3. http://d.wanfangdata.com.cn/Periodical/lcxewkzz201104020
|
[2] |
Seeger RC. Immunology and immunotherapy of neuroblastoma[J]. Semin Cancer Biol, 2011, 21(4): 229-37. doi: 10.1016/j.semcancer.2011.09.012
|
[3] |
Pistoia V, Morandi F, Bianchi G, et al. Immunosuppressive microenvironment in neuroblastoma[J]. Front Oncol, 2013, 3: 167. http://d.wanfangdata.com.cn/OAPaper/oai_doaj-articles_1dc1030e2ffd9722fda191e0f1a982b4
|
[4] |
Long AH, Highfill SL, Cui Y, et al. Reduction of MDSCs with All-trans Retinoic Acid Improves CAR Therapy Efficacy for Sarcomas[J]. Cancer Immunol Res, 2016, 4(10): 869-80. doi: 10.1158/2326-6066.CIR-15-0230
|
[5] |
Komohara Y, Takeya M. CAFs and TAMs: maestros of the tumourmicroenvironment[J]. J Pathol, 2017, 241(3): 313-5. doi: 10.1002/path.4824
|
[6] |
Jales A, Falahati R, Mari E, et al. Ganglioside-exposed dendritic cells inhibit T-cell effector function by promoting regulatory cell activity[J]. Immunology, 2011, 132(1): 134-43. doi: 10.1111/j.1365-2567.2010.03348.x
|
[7] |
Xu W, Cai J, Li S, et al. Improving the in vivo persistence, distribution and function of cytotoxic T lymphocytes by inhibiting the tumor immunosuppressive microenvironment[J]. Scand J Immunol, 2013, 78(1): 50-60. doi: 10.1111/sji.2013.78.issue-1
|
[8] |
Cheung NK, Dyer MA. Neuroblastoma: developmental biology, cancer genomics and immunotherapy[J]. Nat Rev Cancer, 2013, 13(6): 397-411. doi: 10.1038/nrc3526
|
[9] |
Gabrilovich DI. Myeloid-Derived Suppressor Cells[J]. Cancer Immunol Res, 2017, 5(1): 3-8. doi: 10.1158/2326-6066.CIR-16-0297
|
[10] |
Chen J, Ye Y, Liu P, et al. Suppression of T cells by myeloid-derived suppressor cells in cancer[J]. Hum Immunol, 2017, 78(2): 113-9. doi: 10.1016/j.humimm.2016.12.001
|
[11] |
Jordan KR, Kapoor P, Spongberg E, et al. Immunosupp-ressive myeloid-derived suppressor cells are increased in splenocytes from cancer patients[J]. Cancer Immunol Immunother, 2017, 66(4): 503-13. doi: 10.1007/s00262-016-1953-z
|
[12] |
Hassin D, Garber OG, Meiraz A, et al. Cytotoxic T lymphocyte perforin and Fas ligand working in concert even when Fas ligand lytic action is still not detectable[J]. Immunology, 2011, 133(2): 190-6. doi: 10.1111/imm.2011.133.issue-2
|
[13] |
Martínez-Lostao L, Anel A, Pardo J. How Do Cytotoxic Lymphocytes Kill Cancer Cells?[J]. Clin Cancer Res, 2015, 21(22): 5047-56. doi: 10.1158/1078-0432.CCR-15-0685
|
[14] |
Voskoboinik I, Whisstock JC, Trapani JA. Perforin and granzymes: function, dysfunction and human pathology[J]. Nat Rev Immunol, 2015, 15(6): 388-400. doi: 10.1038/nri3839
|
[15] |
Kumar R, Avagyan S, Snoeck HW. A quantitative trait locus on chr.4 regulates thymic involution[J]. J Gerontol A Biol Sci Med Sci, 2010, 65(6): 620-5. http://d.wanfangdata.com.cn/OAPaper/oai_pubmedcentral.nih.gov_2904592
|
[16] |
Lustig A, Carter A, Bertak D, et al. Transcriptome analysis of murine thymocytes reveals age-associated changes in thymic gene expression[J]. Int J Med Sci, 2009, 6(1): 51-64. http://d.wanfangdata.com.cn/OAPaper/oai_pubmedcentral.nih.gov_2640475
|