髓源性抑制细胞在乳腺癌发生中的作用及调控机制
|
摘要
髓源性抑制细胞(myeloid-derived suppressor cells,MDSCs)可以削弱癌症免疫治疗的效果,甚至造成治疗失败。在乳腺癌中,MDSCs主要由乳腺癌细胞募集,从而形成抑制抗肿瘤免疫的微环境。此外,MDSCs可以直接与乳腺癌细胞相互作用。研究表明,MDSCs在乳腺癌发生发展中发挥了免疫抑制作用,进而促进肿瘤血管生成,引起肿瘤耐药和肿瘤转移。因此,阻断MDSCs募集并抑制其功能将会改善乳腺癌的免疫治疗效果。本文将MDSCs在乳腺癌中的生物学功能及调控机制作一综述。
Myeloid-derived suppressor cells( MDSCs) could weaken the efficacy of immunotherapy for cancer,and even result in the failure of cancer treatment. In breast cancer,MDSC s are recruited mainly by breast cancer cells forming a tumor-favor microenvironment to suppress the anti-tumor immune response. Besides,MDSC s could directly interact with breast cancer cells. Recent studies reveal that MDSC s can not only promote the growth and development of breast cancer,but also angiogenesis,drug resistance and metastasis through suppressing anti-tumor immune response. Regarding to the pivotal role of MDSC s in breast cancer,eliminating MDSC s and attenuating its activity might facilitate the treatment of breast cancer. This reviewwill focus on reviewing biological functions and regulatory mechanisms of MDSC s in the progress of breast cancer.
Myeloid-derived suppressor cells( MDSCs) could weaken the efficacy of immunotherapy for cancer,and even result in the failure of cancer treatment. In breast cancer,MDSC s are recruited mainly by breast cancer cells forming a tumor-favor microenvironment to suppress the anti-tumor immune response. Besides,MDSC s could directly interact with breast cancer cells. Recent studies reveal that MDSC s can not only promote the growth and development of breast cancer,but also angiogenesis,drug resistance and metastasis through suppressing anti-tumor immune response. Regarding to the pivotal role of MDSC s in breast cancer,eliminating MDSC s and attenuating its activity might facilitate the treatment of breast cancer. This reviewwill focus on reviewing biological functions and regulatory mechanisms of MDSC s in the progress of breast cancer.
引文
[1] Bray F,Ferlay J,Soerjomataram I,et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2018,68:394-424. DOI:10. 3322/caac. 21492.
[2]李树霞,孔庆暖,黄维清,等. PES1蛋白在乳腺癌组织中的表达及临床意义[J].济宁医学院学报,2018,41(3):180-184. DOI:10. 3969/j. issn. 1000-9760.2018. 03. 007.
[3] Gradishar WJ,Anderson BO,Balassanian R,et al. Breast cancer,bersion 4. 2017,NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Net,2018,16(3):310-320. DOI:10. 6004/jnccn. 2018. 0012.
[4] Gabrilovich DI. Myeloid-derived suppressor cells[J].Cancer Immunol Res,2017,5(1):3-8. DOI:10. 1158/2326-6066. cir-16-0297.
[5] Chung W,Eum HH,Lee HO,et al. Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer[J]. Nat Commun,2017,8:15081. DOI:10. 1038/ncomms15081.
[6] Valanparambil RM,Tam M,Gros PP,et al. IRF-8 regulates expansion of myeloid-derived suppressor cells and Foxp3+regulatory T cells and modulates Th2 immune responses to gastrointestinal nematode infection[J].PLo S Pathog,2017,13(10):e1006647. DOI:10. 1371/journal. ppat. 1006647.
[7] Chiodoni C,Sangaletti S,Colombo MP. Matricellular proteins tune myeloid-derived suppressor cell recruitment and function in breast cancer[J]. J Leukoc Biol,2017,102(2):287-292. DOI:10. 1189/jlb. 3MR1016-447R.
[8] Simpson KD,Templeton DJ,Cross JV. Macrophage migration inhibitory factor promotes tumor growth and metastasis by inducing myeloid-derived suppressor cells in the tumor microenvironment[J]. J Immunol,2012,189(12):5533-5540. DOI:10. 4049/jimmunol. 1201161.
[9] Zou W,Bai Y,Wang X,et al. PERK-Phosphorylated e IF2alpha pathway suppresses tumor metastasis through downregulating expression of programmed death ligand1 and CXCL5 in triple-negative breast cancer[J].Cancer Biother Radiopharm,2017,32(8):282-287.DOI:10. 1089/cbr. 2017. 2237.
[10] Bauer D,Redmon N,Mazzio E,et al. Apigenin inhibits TNFalpha/IL-1alpha-induced CCL2 release through IKBK-epsilon signaling in MDA-MB-231 human breast cancer cells[J]. PLo S One,2017,12(4):e0175558.DOI:10. 1371/journal. pone. 0175558.
[11] Tanaka T,Kajiwara T,Torigoe T,et al. Cancer-associated oxidoreductase ERO1-alpha drives the production of tumor-promoting myeloid-derived suppressor cells via oxidative protein folding[J]. J Immunol,2015,194(4):2004-2010. DOI:10. 4049/jimmunol. 1402538.
[12] Mundy-Bosse BL,Thornton LM,Yang HC,et al. Psychological stress is associated with altered levels of myeloidderived suppressor cells in breast cancer patients[J].Cell Immunol,2011,270(1):80-87. DOI:10. 1016/j.cellimm. 2011. 04. 003.
[13] Tanriover G,Eyinc MB,Aliyev E,et al. Presence of S100A8/Gr1-positive myeloid-derived suppressor cells in primary tumors and visceral organs invaded by breast carcinoma cells[J]. Clin Breast Cancer,2018,18(5):e1067-e1076. DOI:10. 1016/j. clbc. 2018. 03. 013.
[14] Wei L,Zhu S,Li M,et al. High indoleamine 2,3-dioxygenase is correlated with microvessel density and worse prognosis in breast cancer[J]. Front Immunol,2018,9:724. DOI:10. 3389/fimmu. 2018. 00724.
[15] Meyer MA,Baer JM,Knolhoff BL,et al. Breast and pancreatic cancer interrupt IRF8-dependent dendritic cell development to overcome immune surveillance[J]. Nat Commun,2018,9(1):1250. DOI:10. 1038/s41467-018-03600-6.
[16] Di Cara G,Marabeti MR,Musso R,et al. New insights into the occurrence of matrix metalloproteases-2 and-9 in a cohort of breast cancer patients and proteomic correlations[J]. Cells,2018,7(8):89. DOI:10. 3390/cells7080089.
[17] Umansky V,Blattner C,Fleming V,et al. Myeloid-derived suppressor cells and tumor escape from immune surveillance[J]. Semin Immunopathol,2017,39(3):295-305. DOI:10. 1007/s00281-016-0597-6.
[18] Sawant A,Ponnazhagan S. Myeloid-derived suppressor cells as a novel target for the control of osteolytic bone disease[J]. Oncoimmunology,2013,2(5):e24064.DOI:10. 4161/onci. 24064.
[19] Liao F,Liu L,Luo E,et al. Curcumin enhances antitumor immune response in tongue squamous cell carcinoma[J]. Arch Oral Biol,2018,92:32-37. DOI:10.1016/j. archoralbio. 2018. 04. 015.
[20] Cao Y,Slaney CY,Bidwell BN,et al. BMP4 inhibits breast cancer metastasis by blocking myeloid-derived suppressor cell activity[J]. Cancer Res,2014,74(18):5091-5102. DOI:10. 1158/0008-5472. can-13-3171.
[21] Secondini C,Coquoz O,Spagnuolo L,et al. Arginase inhibition suppresses lung metastasis in the 4T1 breast cancer model independently of the immunomodulatory and anti-metastatic effects of VEGFR-2 blockade[J].Oncoimmunology,2017,6(6):e1316437. DOI:10.1080/2162402x. 2017. 1316437.
[22] Kumar R,de Mooij T,Peterson TE,et al. Modulating glioma-mediated myeloid-derived suppressor cell development with sulforaphane[J]. PLo S One,2017,12(6):e0179012. DOI:10. 1371/journal. pone. 0179012.
[23] Thakur A,Schalk D,Sarkar SH,et al. A Th1 cytokineenriched microenvironment enhances tumor killing by activated T cells armed with bispecific antibodies and inhibits the development of myeloid-derived suppressor cells[J]. Cancer Immunol Immunother,2012,61(4):497-509. DOI:10. 1007/s00262-011-1116-1.
[24] Payne KK,Zoon CK,Wan W,et al. Peripheral blood mononuclear cells of patients with breast cancer can be reprogrammed to enhance anti-HER-2/neu reactivity and overcome myeloid-derived suppressor cells[J].Breast Cancer Res Treat,2013,142(1):45-57. DOI:10. 1007/s10549-013-2733-5.
[25] Alizadeh D,Trad M,Hanke NT,et al. Doxorubicin eliminates myeloid-derived suppressor cells and enhances the efficacy of adoptive T-cell transfer in breast cancer[J].Cancer Res,2014,74(1):104-118. DOI:10. 1158/0008-5472. can-13-1545.
[26] Yu J,Du W,Yan F,et al. Myeloid-derived suppressor cells suppress antitumor immune responses through IDO expression and correlate with lymph node metastasis in patients with breast cancer[J]. J Immunol,2013,190(7):3783-3797. DOI:10. 4049/jimmunol. 1201449.
[2]李树霞,孔庆暖,黄维清,等. PES1蛋白在乳腺癌组织中的表达及临床意义[J].济宁医学院学报,2018,41(3):180-184. DOI:10. 3969/j. issn. 1000-9760.2018. 03. 007.
[3] Gradishar WJ,Anderson BO,Balassanian R,et al. Breast cancer,bersion 4. 2017,NCCN clinical practice guidelines in oncology[J]. J Natl Compr Canc Net,2018,16(3):310-320. DOI:10. 6004/jnccn. 2018. 0012.
[4] Gabrilovich DI. Myeloid-derived suppressor cells[J].Cancer Immunol Res,2017,5(1):3-8. DOI:10. 1158/2326-6066. cir-16-0297.
[5] Chung W,Eum HH,Lee HO,et al. Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer[J]. Nat Commun,2017,8:15081. DOI:10. 1038/ncomms15081.
[6] Valanparambil RM,Tam M,Gros PP,et al. IRF-8 regulates expansion of myeloid-derived suppressor cells and Foxp3+regulatory T cells and modulates Th2 immune responses to gastrointestinal nematode infection[J].PLo S Pathog,2017,13(10):e1006647. DOI:10. 1371/journal. ppat. 1006647.
[7] Chiodoni C,Sangaletti S,Colombo MP. Matricellular proteins tune myeloid-derived suppressor cell recruitment and function in breast cancer[J]. J Leukoc Biol,2017,102(2):287-292. DOI:10. 1189/jlb. 3MR1016-447R.
[8] Simpson KD,Templeton DJ,Cross JV. Macrophage migration inhibitory factor promotes tumor growth and metastasis by inducing myeloid-derived suppressor cells in the tumor microenvironment[J]. J Immunol,2012,189(12):5533-5540. DOI:10. 4049/jimmunol. 1201161.
[9] Zou W,Bai Y,Wang X,et al. PERK-Phosphorylated e IF2alpha pathway suppresses tumor metastasis through downregulating expression of programmed death ligand1 and CXCL5 in triple-negative breast cancer[J].Cancer Biother Radiopharm,2017,32(8):282-287.DOI:10. 1089/cbr. 2017. 2237.
[10] Bauer D,Redmon N,Mazzio E,et al. Apigenin inhibits TNFalpha/IL-1alpha-induced CCL2 release through IKBK-epsilon signaling in MDA-MB-231 human breast cancer cells[J]. PLo S One,2017,12(4):e0175558.DOI:10. 1371/journal. pone. 0175558.
[11] Tanaka T,Kajiwara T,Torigoe T,et al. Cancer-associated oxidoreductase ERO1-alpha drives the production of tumor-promoting myeloid-derived suppressor cells via oxidative protein folding[J]. J Immunol,2015,194(4):2004-2010. DOI:10. 4049/jimmunol. 1402538.
[12] Mundy-Bosse BL,Thornton LM,Yang HC,et al. Psychological stress is associated with altered levels of myeloidderived suppressor cells in breast cancer patients[J].Cell Immunol,2011,270(1):80-87. DOI:10. 1016/j.cellimm. 2011. 04. 003.
[13] Tanriover G,Eyinc MB,Aliyev E,et al. Presence of S100A8/Gr1-positive myeloid-derived suppressor cells in primary tumors and visceral organs invaded by breast carcinoma cells[J]. Clin Breast Cancer,2018,18(5):e1067-e1076. DOI:10. 1016/j. clbc. 2018. 03. 013.
[14] Wei L,Zhu S,Li M,et al. High indoleamine 2,3-dioxygenase is correlated with microvessel density and worse prognosis in breast cancer[J]. Front Immunol,2018,9:724. DOI:10. 3389/fimmu. 2018. 00724.
[15] Meyer MA,Baer JM,Knolhoff BL,et al. Breast and pancreatic cancer interrupt IRF8-dependent dendritic cell development to overcome immune surveillance[J]. Nat Commun,2018,9(1):1250. DOI:10. 1038/s41467-018-03600-6.
[16] Di Cara G,Marabeti MR,Musso R,et al. New insights into the occurrence of matrix metalloproteases-2 and-9 in a cohort of breast cancer patients and proteomic correlations[J]. Cells,2018,7(8):89. DOI:10. 3390/cells7080089.
[17] Umansky V,Blattner C,Fleming V,et al. Myeloid-derived suppressor cells and tumor escape from immune surveillance[J]. Semin Immunopathol,2017,39(3):295-305. DOI:10. 1007/s00281-016-0597-6.
[18] Sawant A,Ponnazhagan S. Myeloid-derived suppressor cells as a novel target for the control of osteolytic bone disease[J]. Oncoimmunology,2013,2(5):e24064.DOI:10. 4161/onci. 24064.
[19] Liao F,Liu L,Luo E,et al. Curcumin enhances antitumor immune response in tongue squamous cell carcinoma[J]. Arch Oral Biol,2018,92:32-37. DOI:10.1016/j. archoralbio. 2018. 04. 015.
[20] Cao Y,Slaney CY,Bidwell BN,et al. BMP4 inhibits breast cancer metastasis by blocking myeloid-derived suppressor cell activity[J]. Cancer Res,2014,74(18):5091-5102. DOI:10. 1158/0008-5472. can-13-3171.
[21] Secondini C,Coquoz O,Spagnuolo L,et al. Arginase inhibition suppresses lung metastasis in the 4T1 breast cancer model independently of the immunomodulatory and anti-metastatic effects of VEGFR-2 blockade[J].Oncoimmunology,2017,6(6):e1316437. DOI:10.1080/2162402x. 2017. 1316437.
[22] Kumar R,de Mooij T,Peterson TE,et al. Modulating glioma-mediated myeloid-derived suppressor cell development with sulforaphane[J]. PLo S One,2017,12(6):e0179012. DOI:10. 1371/journal. pone. 0179012.
[23] Thakur A,Schalk D,Sarkar SH,et al. A Th1 cytokineenriched microenvironment enhances tumor killing by activated T cells armed with bispecific antibodies and inhibits the development of myeloid-derived suppressor cells[J]. Cancer Immunol Immunother,2012,61(4):497-509. DOI:10. 1007/s00262-011-1116-1.
[24] Payne KK,Zoon CK,Wan W,et al. Peripheral blood mononuclear cells of patients with breast cancer can be reprogrammed to enhance anti-HER-2/neu reactivity and overcome myeloid-derived suppressor cells[J].Breast Cancer Res Treat,2013,142(1):45-57. DOI:10. 1007/s10549-013-2733-5.
[25] Alizadeh D,Trad M,Hanke NT,et al. Doxorubicin eliminates myeloid-derived suppressor cells and enhances the efficacy of adoptive T-cell transfer in breast cancer[J].Cancer Res,2014,74(1):104-118. DOI:10. 1158/0008-5472. can-13-1545.
[26] Yu J,Du W,Yan F,et al. Myeloid-derived suppressor cells suppress antitumor immune responses through IDO expression and correlate with lymph node metastasis in patients with breast cancer[J]. J Immunol,2013,190(7):3783-3797. DOI:10. 4049/jimmunol. 1201449.