Tumor-Produced Interleukin-8 Attracts Human Myeloid-Derived Suppressor Cells and Elicits Extrusion of Neutrophil Extracellular Traps (NETs)
Tóm tắt
Purpose: Myeloid-derived suppressor cells (MDSC) are considered an important T-cell immunosuppressive component in cancer-bearing hosts. The factors that attract these cells to the tumor microenvironment are poorly understood. IL8 (CXCL8) is a potent chemotactic factor for neutrophils and monocytes.
Experimental Design: MDSC were characterized and sorted by multicolor flow cytometry on ficoll-gradient isolated blood leucokytes from healthy volunteers (n = 10) and advanced cancer patients (n = 28). In chemotaxis assays, sorted granulocytic and monocytic MDSC were tested in response to recombinant IL8, IL8 derived from cancer cell lines, and patient sera. Neutrophil extracellular traps (NETs) formation was assessed by confocal microscopy, fluorimetry, and time-lapse fluorescence confocal microscopy on short-term MDSC cultures.
Results: IL8 chemoattracts both granulocytic (GrMDSC) and monocytic (MoMDSC) human MDSC. Monocytic but not granulocytic MDSC exerted a suppressor activity on the proliferation of autologous T cells isolated from the circulation of cancer patients. IL8 did not modify the T-cell suppressor activity of human MDSC. However, IL8 induced the formation of NETs in the GrMDSC subset.
Conclusions: IL8 derived from tumors contributes to the chemotactic recruitment of MDSC and to their functional control. Clin Cancer Res; 22(15); 3924–36. ©2016 AACR.
Từ khóa
Tài liệu tham khảo
Baggiolini, 1989, Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils, J Clin Invest, 84, 1045, 10.1172/JCI114265
Sanmamed, 2014, Serum interleukin-8 reflects tumor burden and treatment response across malignancies of multiple tissue origins, Clin Cancer Res, 20, 5697, 10.1158/1078-0432.CCR-13-3203
Infanger, 2013, Glioblastoma stem cells are regulated by interleukin-8 signaling in a tumoral perivascular niche, Cancer Res, 73, 7079, 10.1158/0008-5472.CAN-13-1355
Kotyza, 2012, Interleukin-8 (CXCL8) in tumor associated non-vascular extracellular fluids: its diagnostic and prognostic values. A review, Int J Biol Markers, 27, 169, 10.5301/JBM.2012.9261
Singh, 2013, Recent advances reveal IL-8 signaling as a potential key to targeting breast cancer stem cells, Breast Cancer Res, 15, 210, 10.1186/bcr3436
Walz, 1987, Purification and amino acid sequencing of NAF, a novel neutrophil-activating factor produced by monocytes, Biochem Biophys Res Commun, 149, 755, 10.1016/0006-291X(87)90432-3
Waugh, 2008, The interleukin-8 pathway in cancer, Clin Cancer Res, 14, 6735, 10.1158/1078-0432.CCR-07-4843
Xie, 2001, Interleukin-8 and human cancer biology, Cytokine Growth Factor Rev, 12, 375, 10.1016/S1359-6101(01)00016-8
Yuan, 2005, The role of interleukin-8 in cancer cells and microenvironment interaction, Front Biosci, 10, 853, 10.2741/1579
Alfaro, 2011, Carcinoma-derived interleukin-8 disorients dendritic cell migration without impairing T-cell stimulation, PLoS One, 6, e17922, 10.1371/journal.pone.0017922
Fan, 2007, Murine CXCR1 is a functional receptor for GCP-2/CXCL6 and interleukin-8/CXCL8, J Biol Chem, 282, 11658, 10.1074/jbc.M607705200
Gordon, 2010, Alternative activation of macrophages: mechanism and functions, Immunity, 32, 593, 10.1016/j.immuni.2010.05.007
Noy, 2014, Tumor-associated macrophages: from mechanisms to therapy, Immunity, 41, 49, 10.1016/j.immuni.2014.06.010
Ferrara, 2010, Role of myeloid cells in vascular endothelial growth factor-independent tumor angiogenesis, Curr Opin Hematol, 17, 219
Mantovani, 2011, Cancer-promoting tumor-associated macrophages: new vistas and open questions, Eur J Immunol, 41, 2522, 10.1002/eji.201141894
Gabrilovich, 2012, Coordinated regulation of myeloid cells by tumours, Nat Rev Immunol, 12, 253, 10.1038/nri3175
Arina, 2015, Myeloid-derived suppressor cell impact on endogenous and adoptively transferred T cells, Curr Opin Immunol, 33, 120, 10.1016/j.coi.2015.02.006
Berraondo, 2007, Eradication of large tumors in mice by a tritherapy targeting the innate, adaptive, and regulatory components of the immune system, Cancer Res, 67, 8847, 10.1158/0008-5472.CAN-07-0321
Ugel, 2009, Therapeutic targeting of myeloid-derived suppressor cells, Curr Opin Pharmacol, 9, 470, 10.1016/j.coph.2009.06.014
Condamine, 2015, Regulation of tumor metastasis by myeloid-derived suppressor cells, Annu Rev Med, 66, 97, 10.1146/annurev-med-051013-052304
Kitano, 2014, Computational algorithm-driven evaluation of monocytic myeloid-derived suppressor cell frequency for prediction of clinical outcomes, Cancer Immunol Res, 2, 812, 10.1158/2326-6066.CIR-14-0013
Kotsakis, 2012, Myeloid-derived suppressor cell measurements in fresh and cryopreserved blood samples, J Immunol Methods, 381, 14, 10.1016/j.jim.2012.04.004
Nagaraj, 2010, Myeloid-derived suppressor cells in human cancer, Cancer J, 16, 348, 10.1097/PPO.0b013e3181eb3358
Pak, 1995, Mechanisms of immune suppression in patients with head and neck cancer: presence of CD34(+) cells which suppress immune functions within cancers that secrete granulocyte-macrophage colony-stimulating factor, Clin Cancer Res, 1, 95
Poschke, 2012, On the armament and appearances of human myeloid-derived suppressor cells, Clin Immunol, 144, 250, 10.1016/j.clim.2012.06.003
Kalathil, 2013, Higher frequencies of GARP(+)CTLA-4(+)Foxp3(+) T regulatory cells and myeloid-derived suppressor cells in hepatocellular carcinoma patients are associated with impaired T-cell functionality, Cancer Res, 73, 2435, 10.1158/0008-5472.CAN-12-3381
Pico de Coana, 2014, Myeloid-derived suppressor cells and their role in CTLA-4 blockade therapy, Cancer Immunol Immunother, 63, 977, 10.1007/s00262-014-1570-7
Weide, 2014, Myeloid-derived suppressor cells predict survival of patients with advanced melanoma: comparison with regulatory T cells and NY-ESO-1- or melan-A-specific T cells, Clin Cancer Res, 20, 1601, 10.1158/1078-0432.CCR-13-2508
Feijoo, 2005, Dendritic cells delivered inside human carcinomas are sequestered by interleukin-8, Int J Cancer, 116, 275, 10.1002/ijc.21046
Brinkmann, 2004, Neutrophil extracellular traps kill bacteria, Science, 303, 1532, 10.1126/science.1092385
Brinkmann, 2012, Neutrophil extracellular traps: is immunity the second function of chromatin?, J Cell Biol, 198, 773, 10.1083/jcb.201203170
Clark, 2007, Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood, Nat Med, 13, 463, 10.1038/nm1565
Pilsczek, 2010, A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus, J Immunol, 185, 7413, 10.4049/jimmunol.1000675
Urban, 2009, Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans, PLoS Pathog, 5, e1000639, 10.1371/journal.ppat.1000639
Sangaletti, 2012, Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated autoimmunity, Blood, 120, 3007, 10.1182/blood-2012-03-416156
Cools-Lartigue, 2013, Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis, J Clin Invest, 67484
Bizzarri, 2006, ELR+ CXC chemokines and their receptors (CXC chemokine receptor 1 and CXC chemokine receptor 2) as new therapeutic targets, Pharmacol Ther, 112, 139, 10.1016/j.pharmthera.2006.04.002
Citro, 2012, CXCR1/2 inhibition enhances pancreatic islet survival after transplantation, J Clin Invest, 122, 3647, 10.1172/JCI63089
Bronte, 2003, IL-4-induced arginase 1 suppresses alloreactive T cells in tumor-bearing mice, J Immunol, 170, 270, 10.4049/jimmunol.170.1.270
Ochoa, 2012, Liver gene transfer of interkeukin-15 constructs that become part of circulating high density lipoproteins for immunotherapy, PLoS One, 7, e52370, 10.1371/journal.pone.0052370
Ochoa, 2013, Antitumor immunotherapeutic and toxic properties of an HDL-conjugated chimeric IL-15 fusion protein, Cancer Res, 73, 139, 10.1158/0008-5472.CAN-12-2660
Citro, 2015, CXCR1/2 inhibition blocks and reverses type 1 diabetes in mice, Diabetes, 64, 1329, 10.2337/db14-0443
Gallina, 2006, Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells, J Clin Invest, 116, 2777, 10.1172/JCI28828
Serafini, 2004, Derangement of immune responses by myeloid suppressor cells, Cancer Immunol Immunother, 53, 64, 10.1007/s00262-003-0443-2
Di Mitri, 2014, Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer, Nature, 515, 134, 10.1038/nature13638
Lesokhin, 2012, Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment, Cancer Res, 72, 876, 10.1158/0008-5472.CAN-11-1792
Gentles, 2015, The prognostic landscape of genes and infiltrating immune cells across human cancers, Nat Med, 21, 938, 10.1038/nm.3909
Yalavarthi, 2015, Antiphospholipid antibodies promote the release of neutrophil extracellular traps: a new mechanism of thrombosis in the antiphospholipid syndrome, Arthritis Rheumatol, 67, 2990, 10.1002/art.39247
Tanaka, 2014, In vivo characterization of neutrophil extracellular traps in various organs of a murine sepsis model, PLoS One, 9, e111888, 10.1371/journal.pone.0111888
Highfill, 2014, Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy, Sci Transl Med, 6, 237ra67, 10.1126/scitranslmed.3007974