Roles of Myeloid-Derived Suppressor Cells in Cancer Metastasis: Immunosuppression and Beyond

Beury DW, Parker KH, Nyandjo M et al (2014) Cross-talk among myeloid-derived suppressor cells, macrophages, and tumor cells impacts the inflammatory milieu of solid tumors. J Leukoc Biol 96:1109–1118 Bianchi G, Borgonovo G, Pistoia V et al (2011) Immunosuppressive cells and tumour microenvironment: focus on mesenchymal stem cells and myeloid derived suppressor cells. Histol Histopathol 26:941–951 Binsfeld M, Muller J, Lamour V et al (2016) Granulocytic myeloid-derived suppressor cells promote angiogenesis in the context of multiple myeloma. Oncotarget 7:37931–37943 Bodogai M, Moritoh K, Lee-Chang C et al (2015) Immunosuppressive and prometastatic functions of myeloid-derived suppressive cells rely upon education from tumor-associated B cells. Cancer Res 75:3456–3465 Boutte AM, Friedman DB, Bogyo M et al (2011) Identification of a myeloid-derived suppressor cell cystatin-like protein that inhibits metastasis. FASEB J 25:2626–2637 Bronte V, Brandau S, Chen SH et al (2016) Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun 7:12150 Catena R, Bhattacharya N, El Rayes T et al (2013) Bone marrow-derived Gr1 + cells can generate a metastasis-resistant microenvironment via induced secretion of thrombospondin-1. Cancer Discov 3:578–589 Chafe SC, Lou Y, Sceneay J et al (2015) Carbonic anhydrase IX promotes myeloid-derived suppressor cell mobilization and establishment of a metastatic niche by stimulating G-CSF production. Cancer Res 75:996–1008 Chen X, Wang L, Li P et al (2018) Dual TGF-beta and PD-1 blockade synergistically enhances MAGE-A3-specific CD8(+) T cell response in esophageal squamous cell carcinoma. Int J Cancer. https://doi.org/10.1002/ijc.31730 Chiang AC, Massagué J (2008) Molecular basis of metastasis. N Engl J Med 359:2814–2823 Choi HS, Ha SY, Kim HM et al (2016) The prognostic effects of tumor infiltrating regulatory T cells and myeloid derived suppressor cells assessed by multicolor flow cytometry in gastric cancer patients. Oncotarget 7:7940–7951 Condamine T, Ramachandran I, Youn JI et al (2015) Regulation of tumor metastasis by myeloid-derived suppressor cells. Annu Rev Med 66:97–110 Condamine T, Dominguez GA, Youn JI et al (2016) Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients. Sci Immunol 1(2):aaf8943 Connolly MK, Mallen-St Clair J, Bedrosian AS et al (2010) Distinct populations of metastases-enabling myeloid cells expand in the liver of mice harboring invasive and preinvasive intra-abdominal tumor. J Leukoc Biol 87:713–725 Costa-Silva B, Aiello NM, Ocean AJ et al (2015) Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol 17:816–826 Cui TX, Kryczek I, Zhao L et al (2013) Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing microRNA101 and suppressing the corepressor CtBP2. Immunity 39:611–621 Dang CV (1999) c-Myc target genes involved in cell growth, apoptosis, and metabolism. Mol Cell Biol 19:1–11 Deng J, Liu Y, Lee H et al (2012) S1PR1-STAT3 signaling is crucial for myeloid cell colonization at future metastatic sites. Cancer Cell 21:642–654 Deng Z, Rong Y, Teng Y et al (2017) Exosomes miR-126a released from MDSC induced by DOX treatment promotes lung metastasis. Oncogene 36:639–651 Drews-Elger K, Iorns E, Dias A et al (2014) Infiltrating S100A8 + myeloid cells promote metastatic spread of human breast cancer and predict poor clinical outcome. Breast Cancer Res Treat 148:41–59 Eisenblaetter M, Flores-Borja F, Lee JJ et al (2017) Visualization of tumor-immune interaction - target-specific imaging of S100A8/A9 reveals pre-metastatic niche establishment. Theranostics 7:2392–2401 Erler JT, Bennewith KL, Cox TR et al (2009) Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell 15:35–44 Finke J, Ko J, Rini B et al (2011) MDSC as a mechanism of tumor escape from sunitinib mediated anti-angiogenic therapy. Int Immunopharmacol 11:856–861 Fortini ME (2009) Notch signaling: the core pathway and its posttranslational regulation. Dev Cell 16:633–647 Gao D, Joshi N, Choi H et al (2012) Myeloid progenitor cells in the premetastatic lung promote metastases by inducing mesenchymal to epithelial transition. Cancer Res 72:1384–1394 Giles AJ, Reid CM, Evans JD et al (2016) Activation of hematopoietic stem/progenitor cells promotes immunosuppression within the pre-metastatic niche. Cancer Res 76:1335–1347 Guo Y, Xu F, Lu T et al (2012) Interleukin-6 signaling pathway in targeted therapy for cancer. Cancer Treat Rev 38:904–910 Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674 Hiratsuka S, Watanabe A, Aburatani H et al (2006) Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol 8:1369–1375 Hiratsuka S, Watanabe A, Sakurai Y et al (2008) The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol 10:1349–1355 Hoechst B, Voigtlaender T, Ormandy L et al (2009) Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology 50:799–807 Hwang HC, Clurman BE (2005) Cyclin E in normal and neoplastic cell cycles. Oncogene 24:2776–2786 Ichikawa M, Williams R, Wang L et al (2011) S100A8/A9 activate key genes and pathways in colon tumor progression. Mol Cancer Res 9:133–148 Iwata T, Kondo Y, Kimura O et al (2016) PD-L1(+)MDSCs are increased in HCC patients and induced by soluble factor in the tumor microenvironment. Sci Rep 6:39296 Jiang J, Guo W, Liang X (2014) Phenotypes, accumulation, and functions of myeloid-derived suppressor cells and associated treatment strategies in cancer patients. Hum Immunol 75:1128–1137 Kalluri R, Weinberg RA (2009) The basics of epithelial–mesenchymal transition. J Clin Invest 119:1420–1428 Kaplan RN, Riba RD, Zacharoulis S et al (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438:820–827 Ko JS, Rayman P, Ireland J et al (2010) Direct and differential suppression of myeloid-derived suppressor cell subsets by sunitinib is compartmentally constrained. Cancer Res 70:3526–3536 Kowanetz M, Wu X, Lee J et al (2010) Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+ Ly6C+ granulocytes. Proc Natl Acad Sci USA 107:21248–21255 Kujawski M, Kortylewski M, Lee H et al (2008) Stat3 mediates myeloid cell–dependent tumor angiogenesis in mice. J Clin Invest 118:3367–3377 Leber MF, Efferth T (2009) Molecular principles of cancer invasion and metastasis (review). Int J Oncol 34:881–895 Lee JM, Seo JH, Kim YJ et al (2012) The restoration of myeloid-derived suppressor cells as functional antigen-presenting cells by NKT cell help and all-trans-retinoic acid treatment. Int J Cancer 131:741–751 Lee JM, Kim EK, Seo H et al (2014) Serum amyloid A3 exacerbates cancer by enhancing the suppressive capacity of myeloid-derived suppressor cells via TLR2-dependent STAT3 activation. Eur J Immunol 44:1672–1684 Li F, Tiede B, Massagué J et al (2007) Beyond tumorigenesis: cancer stem cells in metastasis. Cell Res 17:3–14 Li ZL, Ye SB, OuYang LY et al (2015) COX-2 promotes metastasis in nasopharyngeal carcinoma by mediating interactions between cancer cells and myeloid-derived suppressor cells. Oncoimmunology 4:e1044712 Lim SY, Gordon-Weeks A, Allen D et al (2015) Cd11b(+) myeloid cells support hepatic metastasis through down-regulation of angiopoietin-like 7 in cancer cells. Hepatology 62:521–533 Lindau D, Gielen P, Kroesen M et al (2013) The immunosuppressive tumour network: myeloid-derived suppressor cells, regulatory T cells and natural killer T cells. Immunology 138:105–115 Lu C, Redd PS, Lee JR et al (2016) The expression profiles and regulation of PD-L1 in tumor-induced myeloid-derived suppressor cells. Oncoimmunology 5:e1247135 Maruhashi T, Kii I, Saito M et al (2010) Interaction between periostin and BMP-1 promotes proteolytic activation of lysyl oxidase. J Biol Chem 285:13294–13303 Marvel D, Gabrilovich DI (2015) Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected. J Clin Invest 125:3356–3364 Mauti LA, Le Bitoux MA, Baumer K et al (2011) Myeloid-derived suppressor cells are implicated in regulating permissiveness for tumor metastasis during mouse gestation. J Clin Invest 121:2794–2807 Moserle L, Casanovas O (2013) Anti-angiogenesis and metastasis: a tumour and stromal cell alliance. J Intern Med 273:128–137 Motallebnezhad M, Jadidi-Niaragh F, Qamsari ES et al (2016) The immunobiology of myeloid-derived suppressor cells in cancer. Tumour Biol 37:1387–1406 Mucha J, Majchrzak K, Taciak B et al (2014) MDSCs mediate angiogenesis and predispose canine mammary tumor cells for metastasis via IL-28/IL-28RA (IFN-λ) signaling. PLoS One 9:e103249 Murdoch C, Muthana M, Coffelt SB et al (2008) The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer 8:618–631 Noman MZ, Desantis G, Janji B et al (2014) PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med 211:781–790 Obermajer N, Muthuswamy R, Lesnock J et al (2011) Positive feedback between PGE2 and COX2 redirects the differentiation of human dendritic cells toward stable myeloid-derived suppressor cells. Blood 118:5498–5505 Oh K, Lee OY, Shon SY et al (2013) A mutual activation loop between breast cancer cells and myeloid-derived suppressor cells facilitates spontaneous metastasis through IL-6 trans-signaling in a murine model. Breast Cancer Res 15:R79 Olechnowicz SW, Edwards CM (2014) Contributions of the host microenvironment to cancer-induced bone disease. Cancer Res 74:1625–1631 Oskarsson T, Batlle E, Massagué J (2014) Metastatic stem cells: sources, niches, and vital pathways. Cell Stem Cell 14:306–321 Ostrand-Rosenberg S, Sinha P, Beury DW et al (2012) Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression. Semin Cancer Biol 22:275–281 Ouzounova M, Lee E, Piranlioglu R et al (2017) Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade. Nat Commun 8:14979 Pan PY, Ma G, Weber KJ et al (2010) Immune stimulatory receptor CD40 is required for T-cell suppression and T regulatory cell activation mediated by myeloid-derived suppressor cells in cancer. Cancer Res 70:99–108 Panni RZ, Sanford DE, Belt BA et al (2014) Tumor-induced STAT3 activation in monocytic myeloid-derived suppressor cells enhances stemness and mesenchymal properties in human pancreatic cancer. Cancer Immunol Immunother 63:513–528 Papaccio F, Paino F, Regad T et al (2017) Concise review: cancer cells, cancer stem cells, and mesenchymal stem cells: influence in cancer development. Stem Cells Transl Med 6:2115–2125 Park YJ, Song B, Kim YS et al (2013) Tumor microenvironmental conversion of natural killer cells into myeloid-derived suppressor cells. Cancer Res 73:5669–5681 Pruenster M, Vogl T, Roth J et al (2016) S100A8/A9: from basic science to clinical application. Pharmacol Ther 167:120–131 Qu X, Zhuang G, Yu L et al (2012) Induction of Bv8 expression by granulocyte colony-stimulating factor in CD11b+ Gr1+ cells: key role of Stat3 signaling. J Biol Chem 287:19574–19584 Rose-John S (2012) IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6. Int J Biol Sci 8:1237–1247 Rutkowski MR, Stephen TL, Svoronos N et al (2015) Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation. Cancer Cell 27:27–40 Sanchez-Tillo E, de Barrios O, Siles L et al (2011) beta-catenin/TCF4 complex induces the epithelial-to-mesenchymal transition (EMT)-activator ZEB1 to regulate tumor invasiveness. Proc Natl Acad Sci USA 108:19204–19209 Sangaletti S, Tripodo C, Sandri S et al (2014) Osteopontin shapes immunosuppression in the metastatic niche. Cancer Res 74:4706–4719 Sato Y, Shimizu K, Shinga J et al (2015) Characterization of the myeloid-derived suppressor cell subset regulated by NK cells in malignant lymphoma. Oncoimmunology 4:e995541 Sawant A, Deshane J, Jules J et al (2013) Myeloid-derived suppressor cells function as novel osteoclast progenitors enhancing bone loss in breast cancer. Cancer Res 73:672–682 Sceneay J, Chow MT, Chen A et al (2012) Primary tumor hypoxia recruits CD11b+/Ly6Cmed/Ly6G+ immune suppressor cells and compromises NK cell cytotoxicity in the premetastatic niche. Cancer Res 72:3906–3911 Seshadri M, Poduval TB, Sundaram K (1979) Studies on metastases. I. Role of sensitization and immunosuppression. J Natl Cancer Inst 63:1205–1210 Shaw AK, Pickup MW, Chytil A et al (2015) TGFβ signaling in myeloid cells regulates mammary carcinoma cell invasion through fibroblast interactions. PLoS One 10:e0117908 Shen T, Zhou L, Shen H et al (2017) Prognostic value of programmed cell death protein 1 expression on CD8+ T lymphocytes in pancreatic cancer. Sci Rep 7:7848 Shen M, Wang J, Yu W et al (2018) A novel MDSC-induced PD-1(−)PD-L1(+) B-cell subset in breast tumor microenvironment possesses immuno-suppressive properties. Oncoimmunology 7:e1413520 Shi Y, Ou L, Han S et al (2014) Deficiency of Kruppel-like factor KLF4 in myeloid-derived suppressor cells inhibits tumor pulmonary metastasis in mice accompanied by decreased fibrocytes. Oncogenesis 3:e129 Shi H, Zhang J, Han X et al (2017) Recruited monocytic myeloid-derived suppressor cells promote the arrest of tumor cells in the premetastatic niche through an IL-1beta-mediated increase in E-selectin expression. Int J Cancer 140:1370–1383 Shiels MS, Copeland G, Goodman MT et al (2015) Cancer stage at diagnosis in patients infected with the human immunodeficiency virus and transplant recipients. Cancer 121:2063–2071 Shojaei F, Wu X, Zhong C et al (2007a) Bv8 regulates myeloid-cell-dependent tumour angiogenesis. Nature 450:825–831 Shojaei F, Wu X, Malik AK et al (2007b) Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+ Gr1+ myeloid cells. Nat Biotechnol 25:911–920 Shojaei F, Wu X, Qu X et al (2009) G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models. Proc Natl Acad Sci USA 106:6742–6747 Sinha P, Clements VK, Bunt SK et al (2007) Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol 179:977–983 Sinha P, Okoro C, Foell D et al (2008) Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells. J Immunol 181:4666–4675 Solito S, Pinton L, Mandruzzato S (2017) In brief: myeloid-derived suppressor cells in cancer. J Pathol 242:7–9 Song J, Lee J, Kim J et al (2016) Pancreatic adenocarcinoma up-regulated factor (PAUF) enhances the accumulation and functional activity of myeloid-derived suppressor cells (MDSCs) in pancreatic cancer. Oncotarget 7:51840–51853 Stacker SA, Achen MG, Jussila L et al (2002) Lymphangiogenesis and cancer metastasis. Nat Rev Cancer 2:573–583 Steeg PS (2016) Targeting metastasis. Nat Rev Cancer 16:201–218 Supuran CT, Winum JY (2015) Carbonic anhydrase IX inhibitors in cancer therapy: an update. Future Med Chem 7:1407–1414 Terai S, Fushida S, Tsukada T et al (2015) Bone marrow derived “fibrocytes” contribute to tumor proliferation and fibrosis in gastric cancer. Gastric Cancer 18:306–313 Thorn M, Point GR, Burga RA et al (2014) Liver metastases induce reversible hepatic B cell dysfunction mediated by Gr-1+ CD11b+ myeloid cells. J Leukoc Biol 96:883–894 Toh B, Wang X, Keeble J et al (2011) Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. PLoS Biol 9:e1001162 Topalian SL, Drake CG, Pardoll DM (2015) Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 27:450–461 Ugel S, De Sanctis F, Mandruzzato S et al (2015) Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages. J Clin Invest 125:3365–3376 Umansky V, Blattner C, Gebhardt C et al (2016) The role of myeloid-derived suppressor cells (MDSC) in cancer progression. Vaccines 4:E36 Vadrevu SK, Chintala NK, Sharma SK et al (2014) Complement c5a receptor facilitates cancer metastasis by altering T-cell responses in the metastatic niche. Cancer Res 74:3454–3465 van Deventer HW, Palmieri DA, Wu QP et al (2013) Circulating fibrocytes prepare the lung for cancer metastasis by recruiting Ly-6C+ monocytes via CCL2. J Immunol 190:4861–4867 Vrakas CN, O’Sullivan RM, Evans SE et al (2015) The measure of DAMPs and a role for S100A8 in recruiting suppressor cells in breast cancer lung metastasis. Immunol Invest 44:174–188 Wang L, Chang EW, Wong SC et al (2013) Increased myeloid-derived suppressor cells in gastric cancer correlate with cancer stage and plasma S100A8/A9 proinflammatory proteins. J Immunol 190:794–804 Wang Z, Xiong S, Mao Y et al (2016) Periostin promotes immunosuppressive premetastatic niche formation to facilitate breast tumour metastasis. J Pathol 239:484–495 Wang D, Sun H, Wei J et al (2017a) CXCL1 is critical for pre-metastatic niche formation and metastasis in colorectal cancer. Cancer Res 77:3655–3665 Wang Q, Liu F, Liu L (2017b) Prognostic significance of PD-L1 in solid tumor: an updated meta-analysis. Medicine (Baltimore) 96:e6369 Welcker M, Clurman BE (2008) FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat Rev Cancer 8:83–93 Wen SW, Sceneay J, Lima LG et al (2016) The biodistribution and immune suppressive effects of breast cancer-derived exosomes. Cancer Res 76:6816–6827 Wong CC, Gilkes DM, Zhang H et al (2011) Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation. Proc Natl Acad Sci USA 108:16369–16374 Wyczechowska D et al (2015) Isolation and characterization of human MDSC from peripheral blood of patients with various malignancies (TUM6P. 971). J Immunol 194(1 Supplement):141.119–141.119 Yamashita YM, Yuan H, Cheng J et al (2010) Polarity in stem cell division: asymmetric stem cell division in tissue homeostasis. Cold Spring Harb Perspect Biol 2:a001313 Yan J, Huang J (2014) Innate γδT17 cells convert cancer-elicited inflammation into immunosuppression through myeloid-derived suppressor cells. Oncoimmunology 3:e953423 Yan HH, Pickup M, Pang Y et al (2010) Gr-1+ CD11b+ myeloid cells tip the balance of immune protection to tumor promotion in the premetastatic lung. Cancer Res 70:6139–6149 Yan HH, Jiang J, Pang Y et al (2015) CCL9 induced by TGFbeta signaling in myeloid cells enhances tumor cell survival in the premetastatic organ. Cancer Res 75:5283–5298 Yang L, DeBusk LM, Fukuda K et al (2004) Expansion of myeloid immune suppressor Gr+ CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6:409–421 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 Ye XZ, Yu SC, Bian XW (2010) Contribution of myeloid-derived suppressor cells to tumor-induced immune suppression, angiogenesis, invasion and metastasis. J Genet Genomics 37:423–430 Yumimoto K, Akiyoshi S, Ueo H et al (2015) F-box protein FBXW7 inhibits cancer metastasis in a non-cell-autonomous manner. J Clin Invest 125:621–635 Zhang B, Wang Z, Wu L et al (2013a) Circulating and tumor-infiltrating myeloid-derived suppressor cells in patients with colorectal carcinoma. PLoS One 8:e57114 Zhang H, Maric I, DiPrima MJ et al (2013b) Fibrocytes represent a novel MDSC subset circulating in patients with metastatic cancer. Blood 122:1105–1113 Zhang G, Huang H, Zhu Y et al (2015a) A novel subset of B7-H3+ CD14+ HLA-DR-/low myeloid-derived suppressor cells are associated with progression of human NSCLC. Oncoimmunology 4:e977164 Zhang X, Yuan X, Shi H et al (2015b) Exosomes in cancer: small particle, big player. J Hematol Oncol 8:83 Zhang Y, Velez-Delgado A, Mathew E et al (2017) Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer. Gut 66:124–136 Zhao T, Du H, Ding X et al (2015) Activation of mTOR pathway in myeloid-derived suppressor cells stimulates cancer cell proliferation and metastasis in lal(−/−) mice. Oncogene 34:1938–1948 Zhao T, Du H, Blum JS et al (2016a) Critical role of PPARgamma in myeloid-derived suppressor cell-stimulated cancer cell proliferation and metastasis. Oncotarget 7:1529–1543 Zhao T, Yan C, Du H (2016b) Lysosomal acid lipase in mesenchymal stem cell stimulation of tumor growth and metastasis. Oncotarget 7:61121–61135 Zheng R, Chen S, Chen S (2015) Correlation between myeloid-derived suppressor cells and S100A8/A9 in tumor and autoimmune diseases. Int Immunopharmacol 29:919–925