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Role of myeloid derived hematopoietic cells in inflammation and immune tolerance to cancer

Iuliana Shapira, Keith S Sultan, Emanuela Taioli, Annette Lee


Cancer is an organ with tumor cells and tumor microenvironment such as the immune system, stromal fibroblasts, macrophages, smooth muscle cells, endothelial cells all embedded in an extracellular matrix that fibroblasts produce. [1] [2]

Myeloid derived cells in and around tumor help cancer cells survive, grow and spread to new locations where they seed metastasis. [3]

Cancer cells from growing tumors hijack mechanisms used by the normal tissues for wound repair such as the productions of growth and angiogenic factors, matrix metalloproteinases, fibroblasts, cells of myeloid lineage and chemokines to promote their survival and growth. [4-8]

Cells of myeloid lineage origin have a crucial role in malignant organ development by protecting the growing tumor mass from immune recognition [9] hampering the immune rejection of cancer cells. [10]

Malignant tumors recruit cells of myeloid derivation to promote the growing tumor and its invasive abilities. [11] Survival of patients with adenocarcinoma of the breast, colon, lung and prostate is inversely proportional to the number of infiltrating cells of myeloid derivation of tumors. [12-15] Such malignancies are associated with shorter survival and detecting molecular signatures typical for macrophage infiltration such as CD68 in tumors herald poor diverse malignancies. [16,17]. There is two way editing of the growing malignancy and immune system of the affected patient: the malignant process shapes the immune system of the patient and at the same time the immune system of the patient shapes the growing tumor by selecting for the cancer cells resistant to immunodetection to survive and multiply. [18]


immune system, malignancy development, cancer, macrophages, dendritic cells, cancer outcome, T-regulatory cells

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Lanier LL, Sun JC: Do the terms innate and adaptive immunity create conceptual barriers? Nat Rev Immunol 2009, 9:302-303.

PMid:19396937 PMCid:PMC2844347

Deel MD, Kong M, Cross KP, Bertolone SJ: Absolute lymphocyte counts as prognostic indicators for immune thrombocytopenia outcomes in children. Pediatr Blood Cancer 2013, 60:1967-1974.


Pamer E, Cresswell P: Mechanisms of MHC class I--restricted antigen processing. Annu Rev Immunol 1998, 16:323-358.


Wong P, Pamer EG: CD8 T cell responses to infectious pathogens. Annu Rev Immunol 2003, 21:29-70.


Mills CD: Macrophage arginine metabolism to ornithine/urea or nitric oxide/citrulline: a life or death issue. Crit Rev Immunol 2001, 21:399-425.


Irving BA, Weiss A: The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways. Cell 1991, 64:891-901.

Rodriguez PC, Zea AH, DeSalvo J, Culotta KS, Zabaleta J, Quiceno DG, Ochoa JB, Ochoa AC: L-arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes. J Immunol 2003, 171:1232-1239.


Gordon S: Alternative activation of macrophages. Nat Rev Immunol 2003, 3:23-35.


Mantovani A, Sica A, Locati M: Macrophage polarization comes of age. Immunity 2005, 23:344-346.


Borg C, Jalil A, Laderach D, Maruyama K, Wakasugi H, Charrier S, Ryffel B, Cambi A, Figdor C, Vainchenker W, et al.: NK cell activation by dendritic cells (DCs) requires the formation of a synapse leading to IL-12 polarization in DCs. Blood 2004, 104:3267-3275.


Carbone E, Terrazzano G, Ruggiero G, Zanzi D, Ottaiano A, Manzo C, Karre K, Zappacosta S: Recognition of autologous dendritic cells by human NK cells. Eur J Immunol 1999, 29:4022-4029.<4022::AID-IMMU4022>3.0.CO;2-O

Stewart TJ, Abrams SI: How tumours escape mass destruction. Oncogene 2008, 27:5894-5903.


Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, et al.: Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 2004, 10:942-949.


Brown JA, Dorfman DM, Ma FR, Sullivan EL, Munoz O, Wood CR, Greenfield EA, Freeman GJ: Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol 2003, 170:1257-1266.


Wyckoff J, Wang W, Lin EY, Wang Y, Pixley F, Stanley ER, Graf T, Pollard JW, Segall J, Condeelis J: A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res 2004, 64:7022-7029.


Zhou Y, Tang L, Lin M, Xu S, Bai J, Song H: Expression of Cytotoxic T-Lymphocyte Antigen 4 on CD4+ and CD8+ T Cells Is Increased in Acute Lung Injury. DNA Cell Biol 2013.

Merad M, Manz MG: Dendritic cell homeostasis. Blood 2009, 113:3418-3427.

PMid:19176316 PMCid:PMC2668851

Degli-Esposti MA, Smyth MJ: Close encounters of different kinds: dendritic cells and NK cells take centre stage. Nat Rev Immunol 2005, 5:112-124.


Taylor PR, Gordon S: Monocyte heterogeneity and innate immunity. Immunity 2003, 19:2-4.

Steinman RM: The control of immunity and tolerance by dendritic cell. Pathol Biol (Paris) 2003, 51:59-60.

Jarrossay D, Napolitani G, Colonna M, Sallusto F, Lanzavecchia A: Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells. Eur J Immunol 2001, 31:3388-3393.<3388::AID-IMMU3388>3.0.CO;2-Q

Palucka KA, Taquet N, Sanchez-Chapuis F, Gluckman JC: Dendritic cells as the terminal stage of monocyte differentiation. J Immunol 1998, 160:4587-4595.


Chomarat P, Banchereau J, Davoust J, Palucka AK: IL-6 switches the differentiation of monocytes from dendritic cells to macrophages. Nat Immunol 2000, 1:510-514.


Iwamoto S, Iwai S, Tsujiyama K, Kurahashi C, Takeshita K, Naoe M, Masunaga A, Ogawa Y, Oguchi K, Miyazaki A: TNF-alpha drives human CD14+ monocytes to differentiate into CD70+ dendritic cells evoking Th1 and Th17 responses. J Immunol 2007, 179:1449-1457.


Chomarat P, Dantin C, Bennett L, Banchereau J, Palucka AK: TNF skews monocyte differentiation from macrophages to dendritic cells. J Immunol 2003, 171:2262-2269.


Mantovani A, Bottazzi B, Colotta F, Sozzani S, Ruco L: The origin and function of tumor-associated macrophages. Immunol Today 1992, 13:265-270.

Mantovani A, Sozzani S, Locati M, Allavena P, Sica A: Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 2002, 23:549-555.

Schioppa T, Uranchimeg B, Saccani A, Biswas SK, Doni A, Rapisarda A, Bernasconi S, Saccani S, Nebuloni M, Vago L, et al.: Regulation of the chemokine receptor CXCR4 by hypoxia. J Exp Med 2003, 198:1391-1402.

PMid:14597738 PMCid:PMC2194248

De Palma M, Venneri MA, Galli R, Sergi Sergi L, Politi LS, Sampaolesi M, Naldini L: Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 2005, 8:211-226.


Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P, Figueiredo JL, Kohler RH, Chudnovskiy A, Waterman P, et al.: Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 2009, 325:612-616.

PMid:19644120 PMCid:PMC2803111

Morita Y, Moriai T, Takiyama Y, Makino I: Establishment and characterization of a new hamster pancreatic cancer cell line: the biological activity and the binding characteristics of EGF or TGF-alpha. Int J Pancreatol 1998, 23:41-50.


Mantovani A, Allavena P, Sozzani S, Vecchi A, Locati M, Sica A: Chemokines in the recruitment and shaping of the leukocyte infiltrate of tumors. Semin Cancer Biol 2004, 14:155-160.


Van Ginderachter JA, Movahedi K, Hassanzadeh Ghassabeh G, Meerschaut S, Beschin A, Raes G, De Baetselier P: Classical and alternative activation of mononuclear phagocytes: picking the best of both worlds for tumor promotion. Immunobiology 2006, 211:487-501.


Condeelis J, Pollard JW: Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 2006, 124:263-266.


Lin EY, Nguyen AV, Russell RG, Pollard JW: Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J Exp Med 2001, 193:727-740.

PMid:11257139 PMCid:PMC2193412

Wyckoff JB, Wang Y, Lin EY, Li JF, Goswami S, Stanley ER, Segall JE, Pollard JW, Condeelis J: Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res 2007, 67:2649-2656.


Lewis CE, Pollard JW: Distinct role of macrophages in different tumor microenvironments. Cancer Res 2006, 66:605-612.


Serafini P, Meckel K, Kelso M, Noonan K, Califano J, Koch W, Dolcetti L, Bronte V, Borrello I: Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med 2006, 203:2691-2702.

PMid:17101732 PMCid:PMC2118163

Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ: Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 2009, 58:49-59.

PMid:18446337 PMCid:PMC3401888

Hoechst B, Ormandy LA, Ballmaier M, Lehner F, Kruger C, Manns MP, Greten TF, Korangy F: A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4(+)CD25(+)Foxp3(+) T cells. Gastroenterology 2008, 135:234-243.


Ochoa AC, Zea AH, Hernandez C, Rodriguez PC: Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res 2007, 13:721s-726s.


Kusmartsev SA, Li Y, Chen SH: Gr-1+ myeloid cells derived from tumor-bearing mice inhibit primary T cell activation induced through CD3/CD28 costimulation. J Immunol 2000, 165:779-785.


Gabrilovich DI, Bronte V, Chen SH, Colombo MP, Ochoa A, Ostrand-Rosenberg S, Schreiber H: The terminology issue for myeloid-derived suppressor cells. Cancer Res 2007, 67:425; author reply 426.

PMid:17210725 PMCid:PMC1941787

Nagaraj S, Gabrilovich DI: Tumor escape mechanism governed by myeloid-derived suppressor cells. Cancer Res 2008, 68:2561-2563.


Schmielau J, Finn OJ: Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of t-cell function in advanced cancer patients. Cancer Res 2001, 61:4756-4760.


Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, Carbone DP, Gabrilovich DI: Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol 2001, 166:678-689.


Rodriguez PC, Ochoa AC: T cell dysfunction in cancer: role of myeloid cells and tumor cells regulating amino acid availability and oxidative stress. Semin Cancer Biol 2006, 16:66-72.


Serafini P, De Santo C, Marigo I, Cingarlini S, Dolcetti L, Gallina G, Zanovello P, Bronte V: Derangement of immune responses by myeloid suppressor cells. Cancer Immunol Immunother 2004, 53:64-72.


Huang B, Pan PY, Li Q, Sato AI, Levy DE, Bromberg J, Divino CM, Chen SH: Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Res 2006, 66:1123-1131.


Sinha P, Clements VK, Bunt SK, Albelda SM, Ostrand-Rosenberg S: Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol 2007, 179:977-983.


Gabrilovich DI, Chen HL, Girgis KR, Cunningham HT, Meny GM, Nadaf S, Kavanaugh D, Carbone DP: Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Nat Med 1996, 2:1096-1103.


Melani C, Chiodoni C, Forni G, Colombo MP: Myeloid cell expansion elicited by the progression of spontaneous mammary carcinomas in c-erbB-2 transgenic BALB/c mice suppresses immune reactivity. Blood 2003, 102:2138-2145.


Zou W, Machelon V, Coulomb-L'Hermin A, Borvak J, Nome F, Isaeva T, Wei S, Krzysiek R, Durand-Gasselin I, Gordon A, et al.: Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells. Nat Med 2001, 7:1339-1346.


Kryczek I, Lange A, Mottram P, Alvarez X, Cheng P, Hogan M, Moons L, Wei S, Zou L, Machelon V, et al.: CXCL12 and vascular endothelial growth factor synergistically induce neoangiogenesis in human ovarian cancers. Cancer Res 2005, 65:465-472.


Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, McClanahan T, Murphy E, Yuan W, Wagner SN, et al.: Involvement of chemokine receptors in breast cancer metastasis. Nature 2001, 410:50-56.


Yang L, DeBusk LM, Fukuda K, Fingleton B, Green-Jarvis B, Shyr Y, Matrisian LM, Carbone DP, Lin PC: Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 2004, 6:409-421.


Horst AK, Bickert T, Brewig N, Ludewig P, van Rooijen N, Schumacher U, Beauchemin N, Ito WD, Fleischer B, Wagener C, et al.: CEACAM1+ myeloid cells control angiogenesis in inflammation. Blood 2009, 113:6726-6736.


Palmowski M, Salio M, Dunbar RP, Cerundolo V: The use of HLA class I tetramers to design a vaccination strategy for melanoma patients. Immunol Rev 2002, 188:155-163.


Romero P, Dunbar PR, Valmori D, Pittet M, Ogg GS, Rimoldi D, Chen JL, Lienard D, Cerottini JC, Cerundolo V: Ex vivo staining of metastatic lymph nodes by class I major histocompatibility complex tetramers reveals high numbers of antigen-experienced tumor-specific cytolytic T lymphocytes. J Exp Med 1998, 188:1641-1650.

PMid:9802976 PMCid:PMC2212507

Yu P, Lee Y, Liu W, Chin RK, Wang J, Wang Y, Schietinger A, Philip M, Schreiber H, Fu YX: Priming of naive T cells inside tumors leads to eradication of established tumors. Nat Immunol 2004, 5:141-149.


Inagaki A, Ishida T, Ishii T, Komatsu H, Iida S, Ding J, Yonekura K, Takeuchi S, Takatsuka Y, Utsunomiya A, et al.: Clinical significance of serum Th1-, Th2- and regulatory T cells-associated cytokines in adult T-cell leukemia/lymphoma: high interleukin-5 and -10 levels are significant unfavorable prognostic factors. Int J Cancer 2006, 118:3054-3061.


Shojaei F, Wu X, Malik AK, Zhong C, Baldwin ME, Schanz S, Fuh G, Gerber HP, Ferrara N: Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol 2007, 25:911-920.


Kaser A, Winklmayr M, Lepperdinger G, Kreil G: The AVIT protein family. Secreted cysteine-rich vertebrate proteins with diverse functions. EMBO Rep 2003, 4:469-473.

PMid:12728244 PMCid:PMC1319185

Shojaei F, Singh M, Thompson JD, Ferrara N: Role of Bv8 in neutrophil-dependent angiogenesis in a transgenic model of cancer progression. Proc Natl Acad Sci U S A 2008, 105:2640-2645.

PMid:18268320 PMCid:PMC2268189

Shojaei F, Zhong C, Wu X, Yu L, Ferrara N: Role of myeloid cells in tumor angiogenesis and growth. Trends Cell Biol 2008, 18:372-378.


Shojaei F, Wu X, Qu X, Kowanetz M, Yu L, Tan M, Meng YG, Ferrara N: G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models. Proc Natl Acad Sci U S A 2009, 106:6742-6747.

PMid:19346489 PMCid:PMC2665197

Braun S, Pantel K, Muller P, Janni W, Hepp F, Kentenich CR, Gastroph S, Wischnik A, Dimpfl T, Kindermann G, et al.: Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N Engl J Med 2000, 342:525-533.


Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, Chadburn A, Heissig B, Marks W, Witte L, et al.: Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 2001, 7:1194-1201.


Rafii S, Lyden D, Benezra R, Hattori K, Heissig B: Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? Nat Rev Cancer 2002, 2:826-835.


Bertolini F, Shaked Y, Mancuso P, Kerbel RS: The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nat Rev Cancer 2006, 6:835-845.


Gao D, Nolan DJ, Mellick AS, Bambino K, McDonnell K, Mittal V: Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science 2008, 319:195-198.


Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, et al.: VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 2005, 438:820-827.

PMid:16341007 PMCid:PMC2945882

Maruyama K, Ii M, Cursiefen C, Jackson DG, Keino H, Tomita M, Van Rooijen N, Takenaka H, D'Amore PA, Stein-Streilein J, et al.: Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages. J Clin Invest 2005, 115:2363-2372.

PMid:16138190 PMCid:PMC1193872

Jeltsch M, Kaipainen A, Joukov V, Meng X, Lakso M, Rauvala H, Swartz M, Fukumura D, Jain RK, Alitalo K: Hyperplasia of lymphatic vessels in VEGF-C transgenic mice. Science 1997, 276:1423-1425.


Breiteneder-Geleff S, Soleiman A, Kowalski H, Horvat R, Amann G, Kriehuber E, Diem K, Weninger W, Tschachler E, Alitalo K, et al.: Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium. Am J Pathol 1999, 154:385-394.

Kerjaschki D: The crucial role of macrophages in lymphangiogenesis. J Clin Invest 2005, 115:2316-2319.

PMid:16138185 PMCid:PMC1193892

Jeon BH, Jang C, Han J, Kataru RP, Piao L, Jung K, Cha HJ, Schwendener RA, Jang KY, Kim KS, et al.: Profound but dysfunctional lymphangiogenesis via vascular endothelial growth factor ligands from CD11b+ macrophages in advanced ovarian cancer. Cancer Res 2008, 68:1100-1109.


Zeisberger SM, Odermatt B, Marty C, Zehnder-Fjallman AH, Ballmer-Hofer K, Schwendener RA: Clodronate-liposome-mediated depletion of tumour-associated macrophages: a new and highly effective antiangiogenic therapy approach. Br J Cancer 2006, 95:272-281.

PMid:16832418 PMCid:PMC2360657

Iwata C, Kano MR, Komuro A, Oka M, Kiyono K, Johansson E, Morishita Y, Yashiro M, Hirakawa K, Kaminishi M, et al.: Inhibition of cyclooxygenase-2 suppresses lymph node metastasis via reduction of lymphangiogenesis. Cancer Res 2007, 67:10181-10189.


Yu H, Kortylewski M, Pardoll D: Crosstalk between cancer and immune cells: role of STAT3 in the tumour microenvironment. Nat Rev Immunol 2007, 7:41-51.


Dey R, Ji K, Liu Z, Chen L: A cytokine-cytokine interaction in the assembly of higher-order structure and activation of the interleukine-3:receptor complex. PLoS One 2009, 4:e5188.

PMid:19352505 PMCid:PMC2662821

Dedeoglu F, Horwitz B, Chaudhuri J, Alt FW, Geha RS: Induction of activation-induced cytidine deaminase gene expression by IL-4 and CD40 ligation is dependent on STAT6 and NFkappaB. Int Immunol 2004, 16:395-404.


Okada E, Yamazaki M, Tanabe M, Takeuchi T, Nanno M, Oshima S, Okamoto R, Tsuchiya K, Nakamura T, Kanai T, et al.: IL-7 exacerbates chronic colitis with expansion of memory IL-7Rhigh CD4+ mucosal T cells in mice. Am J Physiol Gastrointest Liver Physiol 2005, 288:G745-754.


Andersson A, Yang SC, Huang M, Zhu L, Kar UK, Batra RK, Elashoff D, Strieter RM, Dubinett SM, Sharma S: IL-7 promotes CXCR3 ligand-dependent T cell antitumor reactivity in lung cancer. J Immunol 2009, 182:6951-6958.


Chan DA, Kawahara TL, Sutphin PD, Chang HY, Chi JT, Giaccia AJ: Tumor vasculature is regulated by PHD2-mediated angiogenesis and bone marrow-derived cell recruitment. Cancer Cell 2009, 15:527-538.

PMid:19477431 PMCid:PMC2846696

Hornakova T, Staerk J, Royer Y, Flex E, Tartaglia M, Constantinescu SN, Knoops L, Renauld JC: Acute lymphoblastic leukemia-associated JAK1 mutants activate the Janus kinase/STAT pathway via interleukin-9 receptor alpha homodimers. J Biol Chem 2009, 284:6773-6781.

PMid:19139102 PMCid:PMC2652315

Bollrath J, Phesse TJ, von Burstin VA, Putoczki T, Bennecke M, Bateman T, Nebelsiek T, Lundgren-May T, Canli O, Schwitalla S, et al.: gp130-mediated Stat3 activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis. Cancer Cell 2009, 15:91-102.


Hebenstreit D, Wirnsberger G, Horejs-Hoeck J, Duschl A: Signaling mechanisms, interaction partners, and target genes of STAT6. Cytokine Growth Factor Rev 2006, 17:173-188.


Correia MP, Cardoso EM, Pereira CF, Neves R, Uhrberg M, Arosa FA: Hepatocytes and IL-15: a favorable microenvironment for T cell survival and CD8+ T cell differentiation. J Immunol 2009, 182:6149-6159.


Laurence A, Astoul E, Hanrahan S, Totty N, Cantrell D: Identification of pro-interleukin 16 as a novel target of MAP kinases in activated T lymphocytes. Eur J Immunol 2004, 34:587-597.


Wang L, Yi T, Kortylewski M, Pardoll DM, Zeng D, Yu H: IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med 2009, 206:1457-1464.

PMid:19564351 PMCid:PMC2715087

Sattler A, Wagner U, Rossol M, Sieper J, Wu P, Krause A, Schmidt WA, Radmer S, Kohler S, Romagnani C, et al.: Cytokine-induced human IFN-gamma-secreting effector-memory Th cells in chronic autoimmune inflammation. Blood 2009, 113:1948-1956.


Chada S, Bocangel D, Ramesh R, Grimm EA, Mumm JB, Mhashilkar AM, Zheng M: mda-7/IL24 kills pancreatic cancer cells by inhibition of the Wnt/PI3K signaling pathways: identification of IL-20 receptor-mediated bystander activity against pancreatic cancer. Mol Ther 2005, 11:724-733.


Akamatsu N, Yamada Y, Hasegawa H, Makabe K, Asano R, Kumagai I, Murata K, Imaizumi Y, Tsukasaki K, Tsuruda K, et al.: High IL-21 receptor expression and apoptosis induction by IL-21 in follicular lymphoma. Cancer Lett 2007, 256:196-206.


Ziesche E, Bachmann M, Kleinert H, Pfeilschifter J, Muhl H: The interleukin-22/STAT3 pathway potentiates expression of inducible nitric-oxide synthase in human colon carcinoma cells. J Biol Chem 2007, 282:16006-16015.


Gabrilovich DI, Ostrand-Rosenberg S, Bronte V: Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 12:253-268.

PMid:22437938 PMCid:PMC3587148

Mussai F, De Santo C, Abu-Dayyeh I, Booth S, Quek L, McEwen-Smith RM, Qureshi A, Dazzi F, Vyas P, Cerundolo V: Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment. Blood 2013, 122:749-758.

PMid:23733335 PMCid:PMC3731930



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