Targeting tumor-infiltrating macrophages to combat cancer

Immunotherapy

Volumn 5, Issue 10, 2013, Pages 1075-1087

  Panni, Roheena Z ^a   Linehan, David C ^a,b   Denardo, David G ^a,b  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b USA   (United States)

Author keywords

cancer; CCR2; CSF1R; macrophage; therapeutic

Indexed keywords

AMG 820; BACTERIAL VACCINE; CATHEPSIN B; CD11B ANTIBODY; CD11B ANTIGEN; CD40 LIGAND MONOCLONAL ANTIBODY; CHEMOKINE RECEPTOR CCR2; CHEMOKINE RECEPTOR CCR2 ANTAGONIST; CHEMOKINE RECEPTOR CX3CR1; COLONY STIMULATING FACTOR 1 RECEPTOR; COLONY STIMULATING FACTOR 1 RECEPTOR ANTIBODY; EOTAXIN 2; GEMCITABINE; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; IMC CS 4; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; LYMPHOCYTE ANTIGEN; LYMPHOCYTE ANTIGEN 6C; MACROPHAGE DERIVED CHEMOKINE; MLN 1202; MONOCLONAL ANTIBODY; MONOCYTE CHEMOTACTIC PROTEIN 1; PF 04136309; PHOSPHOTRANSFERASE INHIBITOR; PLX 3397; PLX 7486; STAT3 PROTEIN; THYMUS AND ACTIVATION REGULATED CHEMOKINE; TOCILIZUMAB; TOLL LIKE RECEPTOR AGONIST; TRABECTEDIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN INHIBITOR; VASCULOTROPIN RECEPTOR 2 INHIBITOR;

ADVANCED CANCER; ANTIGEN PRESENTATION; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BREAST CANCER; CANCER PROGNOSIS; CANCER RADIOTHERAPY; CANCER STEM CELL; CANCER SURVIVAL; CELL DIFFERENTIATION; CELL INTERACTION; CELL MIGRATION; CELL SURVIVAL; CHLAMYDOPHILA PSITTACI; ENZYME REGULATION; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; IMMUNOTHERAPY; INFLAMMATORY MONOCYTE; KUPFFER CELL; LEGIONELLA PNEUMOPHILA; LEIOMYOSARCOMA; LIPOSARCOMA; LISTERIA MONOCYTOGENES; MACROPHAGE ACTIVATION; MACROPHAGE MIGRATION; MONOCYTE; MYXOSARCOMA; NONHUMAN; OVARY CANCER; OVERALL SURVIVAL; PANCREAS CANCER; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; RESIDENT MONOCYTE; REVIEW; SHIGELLA FLEXNERI; SIGNAL TRANSDUCTION; SOLID TUMOR; TARGET CELL DESTRUCTION; TISSUE SPECIFICITY; TUMOR ASSOCIATED LEUKOCYTE; TUMOR GROWTH; TUMOR INVASION; TUMOR MICROENVIRONMENT;

ANIMALS; CANCER VACCINES; CELL MOVEMENT; HUMANS; IMMUNOMODULATION; MACROPHAGE ACTIVATION; MACROPHAGES; MOLECULAR TARGETED THERAPY; NEOPLASMS; RECEPTOR, MACROPHAGE COLONY-STIMULATING FACTOR; TUMOR ESCAPE; TUMOR MICROENVIRONMENT;

EID: 84885205350     PISSN: 1750743X     EISSN: 17507448     Source Type: Journal    
DOI: 10.2217/imt.13.102     Document Type: Review

References (113)

1. Balkwill F, Mantovani A. Inflammation and cancer: Back to Virchow? Lancet 357(9255), 539-545 (2001).
2. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 140(6), 883-899 (2010).
3. Bui JD, Schreiber RD. Cancer immunosurveillance, immunoediting and inflammation: Independent or interdependent processes? Curr. Opin. Immunol. 19(2), 203-208 (2007).
4. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 5(12), 953-964 (2005).
5. 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. 23(11), 549-555 (2002).
6. Sica A, Bronte V. Altered macrophage differentiation and immune dysfunction in tumor development. J. Clin. Invest. 117(5), 1155-1166 (2007).
7. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell 141(1), 39-51 (2010).
8. Hashimoto D, Chow A, Noizat C et al. Tissue-resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes. Immunity 38(4), 792-804 (2013).
9. Auffray C, Fogg D, Garfa M et al. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science 317(5838), 666-670 (2007).
10. Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 19(1), 71-82 (2003).
11. Nahrendorf M, Swirski FK, Aikawa E et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J. Exp. Med. 204(12), 3037-3047 (2007).
12. Sanford De , Belt BA, Panni RZ et al. Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer: A role for targeting the CCL2/CCR2 axis. Clin. Cancer Res. 19(13), 3404-3415 (2013).
13. Porembka MR, Mitchem JB, Belt BA et al. Pancreatic adenocarcinoma induces bone marrow mobilization of myeloid-derived suppressor cells which promote primary tumor growth. Cancer Immunol. Immunother. 61(9), 1373-1385 (2012).
14. Lin EY, Nguyen AV, Russell RG, Pollard JW. Colony-stimulating factor promotes progression of mammary tumors to malignancy. J. Exp. Med. 193(6), 727-740 (2001).
15. Groblewska M, Mroczko B, Wereszczynska-Siemiatkowska U, Mysliwiec P, Kedra B, Szmitkowski M. Serum levels of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF) in pancreatic cancer patients. Clin. Chem. Lab. Med. 45(1), 30-34 (2007).
16. Mroczko B, Groblewska M, Wereszczynska-Siemiatkowska U et al. Serum macrophage-colony stimulating factor levels in colorectal cancer patients correlate with lymph node metastasis and poor prognosis. Clin. Chim. Acta 380(1-2), 208-212 (2007).
17. Zhu XD, Zhang JB, Zhuang PY et al. High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. J. Clin. Oncol. 26(16), 2707-2716 (2008).
18. Passlick B, Flieger D, Ziegler-Heitbrock HW. Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood 74(7), 2527-2534 (1989).
19. Wijffels JF, De Rover Z, Beelen RH, Kraal G, van Rooijen N. Macrophage subpopulations in the mouse spleen renewed by local proliferation. Immunobiology 191(1), 52-64 (1994).
20. Cortez-Retamozo V, Etzrodt M, Newton A et al. Origins of tumor-associated macrophages and neutrophils. Proc. Natl Acad. Sci. USA 109(7), 2491-2496 (2012).
21. Martinez FO, Sica A, Mantovani A, Locati M. Macrophage activation and polarization. Front. Biosci. 13, 453-461 (2008).
22. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 25(12), 677-686 (2004).
23. Gerber JS, Mosser DM. Reversing lipopolysaccharide toxicity by ligating the macrophage Fc g receptors. J. Immunol. 166(11), 6861-6868 (2001).
24. Mantovani A. From phagocyte diversity and activation to probiotics: Back to Metchnikoff. Eur. J. Immunol. 38(12), 3269-3273 (2008).
25. Hamilton JA. Colony-stimulating factors in inflammation and autoimmunity. Nat. Rev. Immunol. 8(7), 533-544 (2008).
26. Swann JB, Vesely MD, Silva A et al. Demonstration of inflammation-induced cancer and cancer immunoediting during primary tumorigenesis. Proc. Natl Acad. Sci. USA 105(2), 652-656 (2008).
27. Pollard JW. Macrophages De fine the invasive microenvironment in breast cancer. J. Leukoc. Biol. 84(3), 623-630 (2008).
28. Lin EY, Li JF, Gnatovskiy L et al. Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res. 66(23), 11238-11246 (2006).
29. Ohri CM, Shikotra A, Green RH, Waller DA, Bradding P. The tissue microlocalisation and cellular expression of CD163, VEGF, HLA-DR, iNOS, and MRP 8/14 is correlated to clinical outcome in NSCLC. PLoS ONE 6(7), e21874 (2011).
30. Ohri CM, Shikotra A, Green RH, Waller DA, Bradding P. Macrophages within NSCLC tumour islets are predominantly of a cytotoxic M1 phenotype associated with extended survival. Eur. Respir. J. 33(1), 118-126 (2009).
31. Ma J, Liu L, Che G, Yu N, Dai F, You Z. The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time. BMC Cancer 10, 112 (2010).
32. Mantovani A, Sica A. Macrophages, innate immunity and cancer: Balance, tolerance, and diversity. Curr. Opin. Immunol. 22(2), 231-237 (2010).
33. Mantovani A, Garlanda C, Allavena P. Molecular pathways and targets in cancer-related inflammation. Ann. Med. 42(3), 161-170 (2010).
34. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat. Rev. Immunol. 12(4), 253-268 (2012).
35. Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: Regulators of the tumor microenvironment. Cell 141(1), 52-67 (2010).
36. Reilkoff RA, Bucala R, Herzog EL. Fibrocytes: Emerging effector cells in chronic inflammation. Nat. Rev. Immunol. 11(6), 427-435 (2011).
37. Mason SD, Joyce JA. Proteolytic networks in cancer. Trends Cell. Biol. 21(4), 228-237 (2011).
38. Vasiljeva O, Papazoglou A, Kruger A et al. Tumor cell-derived and macrophage-derived cathepsin B promotes progression and lung metastasis of mammary cancer. Cancer Res. 66(10), 5242-5250 (2006).
39. Heuff G, Oldenburg HS, Boutkan H et al. Enhanced tumour growth in the rat liver after selective elimination of Kupffer cells. Cancer Immunol. Immunother. 37(2), 125-130 (1993).
40. Greten FR, Karin M. The IKK/NF-kB activation pathway-a target for prevention and treatment of cancer. Cancer Lett. 206(2), 193-199 (2004).
41. Savagner P. Leaving the neighborhood: Molecular mechanisms involved during epithelial-mesenchymal transition. Bioessays 23(10), 912-923 (2001).
42. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat. Rev. Cancer 2(6), 442-454 (2002).
43. Lin CY, Lin CJ, Chen KH, Wu JC, Huang SH, Wang SM. Macrophage activation increases the invasive properties of hepatoma cells by destabilization of the adherens junction. FEBS Lett. 580(13), 3042-3050 (2006).
44. Jinushi M, Chiba S, Yoshiyama H et al. Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells. Proc. Natl Acad. Sci. USA 108(30), 12425-12430 (2011).
45. Yang J, Liao D, Chen C et al. Tumor associated macrophages regulate murine breast cancer stem cells through a novel paracrine EGFR/Stat3/Sox-2 signaling pathway. Stem Cells 31(2), 248-258 (2013).
46. Mitchem JB, Brennan DJ, Knolhoff BL et al. Targeting tumor-infiltrating macrophages decreases tumor-initiating cells, relieves immunosuppression, and improves chemotherapeutic responses. Cancer Res. 73(3), 1128-1141 (2013).
47. Roca H, Varsos ZS, Sud S, Craig MJ, Ying C, Pienta KJ. CCL2 and interleukin-6 promote survival of human CD11b+ peripheral blood mononuclear cells and induce M2-type macrophage polarization. J. Biol. Chem. 284(49), 34342-34354 (2009).
48. Zhang J, Lu Y, Pienta KJ. Multiple roles of chemokine (C-C motif ) ligand 2 in promoting prostate cancer growth. J. Natl Cancer Inst. 102(8), 522-528 (2010).
49. Popivanova BK, Kostadinova FI, Furuichi K et al. Blockade of a chemokine, CCL2, reduces chronic colitis-associated carcinogenesis in mice. Cancer Res. 69(19), 7884-7892 (2009).
50. Gazzaniga S, Bravo AI, Guglielmotti A et al. Targeting tumor-associated macrophages and inhibition of MCP-1 reduce angiogenesis and tumor growth in a human melanoma xenograft. J. Invest. Dermatol. 127(8), 2031-2041 (2007).
51. Qian BZ, Li J, Zhang H et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475(7355), 222-225 (2011).
52. Zhu X, Fujita M, Snyder LA, Okada H. Systemic delivery of neutralizing antibody targeting CCL2 for glioma therapy. J. Neurooncol. 104(1), 83-92 (2011).
53. Loberg RD, Ying C, Craig M et al. Targeting CCL2 with systemic delivery of neutralizing antibodies induces prostate cancer tumor regression in vivo. Cancer Res. 67(19), 9417-9424 (2007).
54. Lu Y, Cai Z, Xiao G et al. Monocyte chemotactic protein-1 mediates prostate cancer-induced bone resorption. Cancer Res. 67(8), 3646-3653 (2007).
55. Lu X, Kang Y. Chemokine (C-C motif ) ligand 2 engages CCR2+ stromal cells of monocytic origin to promote breast cancer metastasis to lung and bone. J. Biol. Chem. 284(42), 29087-29096 (2009).
56. Fridlender ZG, Kapoor V, Buchlis G et al. Monocyte chemoattractant protein-1 blockade inhibits lung cancer tumor growth by altering macrophage phenotype and activating CD8+ cells. Am. J. Respir. Cell. Mol. Biol. 44(2), 230-237 (2011).
57. Germano G, Frapolli R, Belgiovine C et al. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell 23(2), 249-262 (2013).
58. Ahn GO, Tseng D, Liao CH, Dorie MJ, Czechowicz A, Brown JM. Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing myeloid cell recruitment. Proc. Natl Acad. Sci. USA 107(18), 8363-8368 (2010).
59. Du R, Lu KV, Petritsch C et al. HIF1a induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell 13(3), 206-220 (2008).
60. Fang HY, Hughes R, Murdoch C et al. Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia. Blood 114(4), 844-859 (2009).
61. Welford AF, Biziato D, Coffelt SB et al. TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice. J. Clin. Invest. 121(5), 1969-1973 (2011).
62. Fischer C, Jonckx B, Mazzone M et al. Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell 131(3), 463-475 (2007).
63. Dineen SP, Lynn KD, Holloway SE et al. Vascular endothelial growth factor receptor 2 mediates macrophage infiltration into orthotopic pancreatic tumors in mice. Cancer Res. 68(11), 4340-4346 (2008).
64. Roland CL, Dineen SP, Lynn KD et al. Inhibition of vascular endothelial growth factor reduces angiogenesis and modulates immune cell infiltration of orthotopic breast cancer xenografts. Mol. Cancer Ther. 8(7), 1761-1771 (2009).
65. De Nardo DG, Brennan DJ, Rexhepaj E et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov. 1(1), 54-67 (2011).
66. Patsialou A, Wyckoff J, Wang Y, Goswami S, Stanley ER, Condeelis JS. Invasion of human breast cancer cells in vivo requires both paracrine and autocrine loops involving the colony-stimulating factor-1 receptor. Cancer Res. 69(24), 9498-9506 (2009).
67. Pyonteck SM, Gadea BB, Wang HW et al. deficiency of the macrophage growth factor CSF-1 disrupts pancreatic neuroendocrine tumor development. Oncogene 31(11), 1459-1467 (2011).
68. Paulus P, Stanley ER, Schafer R, Abraham D, Aharinejad S. Colony-stimulating factor-1 antibody reverses chemoresistance in human MCF-7 breast cancer xenografts. Cancer Res. 66(8), 4349-4356 (2006).
69. Xu J, Escamilla J, Mok S et al. Abrogating the protumorigenic influences of tumor-infiltrating myeloid cells by CSF1R signaling blockade improves the efficacy of radiotherapy in prostate cancer. Cancer Res. 73(9), 2782-2794 (2013).
70. Priceman SJ, Sung JL, Shaposhnik Z et al. Targeting distinct tumor-infiltrating myeloid cells by inhibiting CSF-1 receptor: Combating tumor evasion of antiangiogenic therapy. Blood 115(7), 1461-1471 (2010).
71. Rogers TL, Holen I. Tumour macrophages as potential targets of bisphosphonates. J. Transl. Med. 9, 177 (2011).
72. 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 95(3), 272-281 (2006).
73. Hiraoka K, Zenmyo M, Watari K et al. Inhibition of bone and muscle metastases of lung cancer cells by a Decrease in the number of monocytes/macrophages. Cancer Sci. 99(8), 1595-1602 (2008).
74. Miselis NR, Wu ZJ, van Rooijen N, Kane AB. Targeting tumor-associated macrophages in an orthotopic murine model of diffuse malignant mesothelioma. Mol. Cancer Ther. 7(4), 788-799 (2008).
75. Gnant M, Mlineritsch B, Schippinger W et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N. Engl. J. Med. 360(7), 679-691 (2009).
76. Eidtmann H, De Boer R, Bundred N et al. Efficacy of zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: 36-month results of the ZO-FAST study. Ann. Oncol. 21(11), 2188-2194 (2010).
77. Coleman R, Cook R, Hirsh V, Major P, Lipton A. Zoledronic acid use in cancer patients: More than just supportive care? Cancer 117(1), 11-23 (2011).
78. Tsagozis P, Eriksson F, Pisa P. Zoledronic acid modulates antitumoral responses of prostate cancer-tumor associated macrophages. Cancer Immunol. Immunother. 57(10), 1451-1459 (2008).
79. Giraudo E, Inoue M, Hanahan D. An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J. Clin. Invest. 114(5), 623-633 (2004).
80. Kantarjian H, Shah NP, Hochhaus A et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N. Engl. J. Med. 362(24), 2260-2270 (2010).
81. Bak SP, Walters JJ, Takeya M, Conejo-Garcia JR, Berwin BL. Scavenger receptor-A-targeted leukocyte depletion inhibits peritoneal ovarian tumor progression. Cancer Res. 67(10), 4783-4789 (2007).
82. Pulaski HL, Spahlinger G, Silva IA et al. Identifying alemtuzumab as an anti-myeloid cell antiangiogenic therapy for the treatment of ovarian cancer. J. Transl. Med. 7, 49 (2009).
83. Puig-Kroger A, Sierra-Filardi E, Dominguez-Soto A et al. Folate receptor b is expressed by tumor-associated macrophages and constitutes a marker for M2 anti-inflammatory/regulatory macrophages. Cancer Res. 69(24), 9395-9403 (2009).
84. Kurahara H, Takao S, Kuwahata T et al. Clinical significance of folate receptor b-expressing tumor-associated macrophages in pancreatic cancer. Ann. Surg. Oncol. 19(7), 2264-2271 (2012).
85. Nagai T, Tanaka M, Tsuneyoshi Y et al. Targeting tumor-associated macrophages in an experimental glioma model with a recombinant immunotoxin to folate receptor b. Cancer Immunol. Immunother. 58(10), 1577-1586 (2009).
86. Galmbacher K, Heisig M, Hotz C et al. Shigella mediated depletion of macrophages in a murine breast cancer model is associated with tumor regression. PLoS ONE 5(3), e9572 (2010).
87. Weigert A, Sekar D, Brune B. Tumor-associated macrophages as targets for tumor immunotherapy. Immunotherapy 1(1), 83-95 (2009).
88. Beatty GL, Chiorean EG, Fishman MP et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 331(6024), 1612-1616 (2011).
89. Buhtoiarov IN, Lum HD, Berke G, Sondel PM, Rakhmilevich AL. Synergistic activation of macrophages via CD40 and TLR9 results in T cell independent antitumor effects. J. Immunol. 176(1), 309-318 (2006).
90. Seya T, Shime H, Matsumoto M. TAMable tumor-associated macrophages in response to innate RNA sensing. Oncoimmunology 1(6), 1000-1001 (2012).
91. Shime H, Matsumoto M, Oshiumi H et al. Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors. Proc. Natl Acad. Sci. USA 109(6), 2066-2071 (2012).
92. Hemmi H, Takeuchi O, Kawai T et al. A Toll-like receptor recognizes bacterial DNA. Nature 408(6813), 740-745 (2000).
93. Smith KJ, Hamza S, Skelton H. Topical imidazoquinoline therapy of cutaneous squamous cell carcinoma polarizes lymphoid and monocyte/macrophage populations to a Th1 and M1 cytokine pattern. Clin. Exp. Dermatol. 29(5), 505-512 (2004).
94. Guiducci C, Vicari AP, Sangaletti S, Trinchieri G, Colombo MP. Redirecting in vivo elicited tumor infiltrating macrophages and dendritic cells towards tumor rejection. Cancer Res. 65(8), 3437-3446 (2005).
95. Hagemann T, Lawrence T, Mcneish I et al. Re-educating tumor-associated macrophages by targeting NF-kB. J. Exp. Med. 205(6), 1261-1268 (2008).
96. Dunn GP, Koebel CM, Schreiber RD. Interferons, immunity and cancer immunoediting. Nat. Rev. Immunol. 6(11), 836-848 (2006).
97. Alvaro T, Lejeune M, Camacho FI et al. The presence of STAT1-positive tumor-associated macrophages and their relation to outcome in patients with follicular lymphoma. Haematologica 91(12), 1605-1612 (2006).
98. Hussain SF, Kong LY, Jordan J et al. A novel small molecule inhibitor of signal transducers and activators of transcription 3 reverses immune tolerance in malignant glioma patients. Cancer Res. 67(20), 9630-9636 (2007).
99. Yu AL, Gilman AL, Ozkaynak MF et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N. Engl. J. Med. 363(14), 1324-1334 (2010).
100. Xin H, Zhang C, Herrmann A, Du Y, Figlin R, Yu H. Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells. Cancer Res. 69(6), 2506-2513 (2009).
101. Edwards JP, Emens LA. The multikinase inhibitor sorafenib reverses the suppression of IL-12 and enhancement of IL-10 by PGE(2) in murine macrophages. Int. Immunopharmacol. 10(10), 1220-1228 (2010).
102. Torrero MN, Xia X, Henk W, Yu S, Li S. Stat1 deficiency in the host enhances interleukin-12-mediated tumor regression. Cancer Res. 66(8), 4461-4467 (2006).
103. Van Ginderachter JA, Movahedi K, Van Den Bossche J, De Baetselier P. Macrophages, PPARs, and cancer. PPAR Res. 2008, 169414 (2008).
104. Rolny C, Mazzone M, Tugues S et al. HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF. Cancer Cell 19(1), 31-44 (2011).
105. Chakraborty P, Chatterjee S, Ganguly A et al. Reprogramming of TAM toward proimmunogenic type through regulation of MAP kinases using a redox-active copper chelate. J. Leukoc. Biol. 91(4), 609-619 (2012).
106. Tyagi A, Singh RP, Ramasamy K et al. Growth inhibition and regression of lung tumors by silibinin: Modulation of angiogenesis by macrophage-associated cytokines and nuclear factor-kB and signal transducers and activators of transcription 3. Cancer Prev. Res. (Phila.) 2(1), 74-83 (2009).
107. Vishvakarma NK, Singh SM. Immunopotentiating effect of proton pump inhibitor pantoprazole in a lymphoma-bearing murine host: Implication in antitumor activation of tumor-associated macrophages. Immunol. Lett. 134(1), 83-92 (2010).
108. De Palma M, Lewis CE. Macrophage regulation of tumor responses to anticancer therapies. Cancer Cell 23(3), 277-286 (2013).
109. Kioi M, Vogel H, Schultz G, Hoffman RM, Harsh GR, Brown JM. Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J. Clin. Invest. 120(3), 694-705 (2010).
110. Kozin SV, Kamoun WS, Huang Y, Dawson MR, Jain RK, Duda DG. Recruitment of myeloid but not endothelial precursor cells facilitates tumor regrowth after local irradiation. Cancer Res. 70(14), 5679-5685 (2010).
111. Xu J, Escamilla J, Mok S et al. CSF1R signaling blockade stanches tumor-infiltrating myeloid cells and improves the efficacy of radiotherapy in prostate cancer. Cancer Res. 73(9), 2782-2794 (2013).
112. Tsai CS, Chen FH, Wang CC et al. Macrophages from irradiated tumors express higher levels of iNOS, arginase-I and COX-2, and promote tumor growth. Int. J. Radiat. Oncol. Biol. Phys. 68(2), 499-507 (2007).
113. Chiang CS, Fu SY, Wang SC et al. Irradiation promotes an m2 macrophage phenotype in tumor hypoxia. Front. Oncol. 2, 89 (2012).