A model for cancer-suppressive inflammation

OncoImmunology

Volumn 1, Issue 7, 2012, Pages 1146-1155

  Haabeth, Ole Audun Werner ^a   Bogen, Bjarne ^a   Corthay, Alexandre ^a,b  

^a OSLO UNIVERSITY HOSPITAL   (Norway)

^b UNIVERSITY OF OSLO   (Norway)

Author keywords

Cancer; Inflammation; M1 macrophages; Proinflammatory cytokines; Th1 cells

Indexed keywords

BCG VACCINE; CANCER VACCINE; CPG OLIGODEOXYNUCLEOTIDE; CYCLOPHOSPHAMIDE; DNA VACCINE; GAMMA INTERFERON; INTERLEUKIN 10 ANTIBODY; INTERLEUKIN 1ALPHA; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 6; RECOMBINANT INTERLEUKIN 6; TUMOR NECROSIS FACTOR ALPHA;

ACUTE GRANULOCYTIC LEUKEMIA; ADJUVANT THERAPY; ARTICLE; B CELL LYMPHOMA; BLADDER CANCER; CANCER IMMUNOTHERAPY; CANCER INHIBITION; CANCER PREVENTION; CANCER PROGNOSIS; CANCER SURVIVAL; CARCINOGENICITY; COLON CARCINOMA; DRUG MECHANISM; DRUG POTENTIATION; FRIEND LEUKEMIA; HUMAN; IMMUNOCOMPETENT CELL; INFLAMMATION; LIVER METASTASIS; LUNG CANCER; LUNG CARCINOMA; LUNG METASTASIS; LYMPHOMA; MELANOMA; MYELOMA; NONHUMAN; PLASMACYTOMA; PRIORITY JOURNAL; PROTEIN FUNCTION; SARCOMA; T LYMPHOCYTE; TH1 CELL; TUMOR ASSOCIATED LEUKOCYTE; TUMOR IMMUNITY;

EID: 84876515818     PISSN: 21624011     EISSN: 2162402X     Source Type: Journal    
DOI: 10.4161/onci.21542     Document Type: Article

References (118)

1. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow. Lancet 2001; 357:539-45; PMID:11229684; http://dx.doi.org/10.1016/S0140-6736(00)04046-0.
2. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420:860-7; PMID:12490959; http://dx.doi.org/10.1038/nature01322.
3. Mantovani A, Allavena P, Sica A, Balkwill F. Cancerrelated inflammation. Nature 2008; 454:436-44; PMID:18650914; http://dx.doi.org/10.1038/nature07205.
4. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell 2010; 140:883-99; PMID:20303878; http://dx.doi.org/10.1016/j.cell.2010.01.025.
5. Pelliniemi TT, Irjala K, Mattila K, Pulkki K, Rajamäki A, Tienhaara A, et al.; Finnish Leukemia Group. Immunoreactive interleukin-6 and acute phase proteins as prognostic factors in multiple myeloma. Blood 1995; 85:765-71; PMID:7530507.
6. Preti HA, Cabanillas F, Talpaz M, Tucker SL, Seymour JF, Kurzrock R. Prognostic value of serum interleukin-6 in diffuse large-cell lymphoma. Ann Intern Med 1997; 127:186-94; PMID:9245223.
7. Martín F, Santolaria F, Batista N, Milena A, González-Reimers E, Brito MJ, et al. Cytokine levels (IL-6 and IFN-gamma), acute phase response and nutritional status as prognostic factors in lung cancer. Cytokine 1999; 11:80-6; PMID:10080883; http://dx.doi.org/10.1006/cyto.1998.0398.
8. Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 2001; 48:526-35; PMID:11247898; http://dx.doi.org/10.1136/gut.48.4.526.
9. Polk DB, Peek RM Jr. Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer 2010; 10:403-14; PMID:20495574; http://dx.doi.org/10.1038/nrc2857.
10. Ekström K, Hjalgrim H, Brandt L, Baecklund E, Klareskog L, Ekbom A, et al. Risk of malignant lymphomas in patients with rheumatoid arthritis and in their first-degree relatives. Arthritis Rheum 2003; 48:963-70; PMID:12687538; http://dx.doi.org/10.1002/art.10939.
11. Rothwell PM, Price JF, Fowkes FG, Zanchetti A, Roncaglioni MC, Tognoni G, et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet 2012; 379:1602-12; PMID:22440946; http://dx.doi.org/10.1016/S0140/cimm36(11)61720-0.
12. Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet 2012; 379:1591-601; PMID:22440947; http://dx.doi.org/10.1016/S0140-6736(12)60209-8.
13. Algra AM, Rothwell PM. Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol 2012; 13:518-27; PMID:22440112; http://dx.doi.org/10.1016/S1470-2045(12)70112-2.
14. Lauritzsen GF, Weiss S, Dembic Z, Bogen B. Naive idiotype-specific CD4+ T cells and immunosurveillance of B-cell tumors. Proc Natl Acad Sci USA 1994; 91:5700-4; PMID:7911244; http://dx.doi.org/10.1073/pnas.91.12.5700.
15. Bogen B, Munthe L, Sollien A, Hofgaard P, Omholt H, Dagnaes F, et al. Naive CD4+ T cells confer idiotypespecific tumor resistance in the absence of antibodies. Eur J Immunol 1995; 25:3079-86; PMID:7489746; http://dx.doi.org/10.1002/eji.1830251114.
16. Corthay A, Skovseth DK, Lundin KU, Røsjø E, Omholt H, Hofgaard PO, et al. Primary antitumor immune response mediated by CD4+ T cells. Immunity 2005; 22:371-83; PMID:15780993; http://dx.doi.org/10.1016/j.immuni.2005.02.003.
17. Corthay A, Lundin KU, Lorvik KB, Hofgaard PO, Bogen B. Secretion of tumor-specific antigen by myeloma cells is required for cancer immunosurveillance by CD4+ T cells. Cancer Res 2009; 69:5901-7; PMID:19567679; http://dx.doi.org/10.1158/0008-5472.CAN-08-4816.
18. Lorvik KB, Bogen B, Corthay A. Fingolimod blocks immunosurveillance of myeloma and B-cell lymphoma resulting in cancer development in mice. Blood 2012; 119:2176-7; PMID:22383793; http://dx.doi.org/10.1182/blood-2011-10-388892.
19. Haabeth OA, Lorvik KB, Hammarström C, Donaldson IM, Haraldsen G, Bogen B, et al. Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer. Nat Commun 2011; 2:240; PMID:21407206; http://dx.doi.org/10.1038/ncomms1239.
20. Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol 2000; 164:6166-73; PMID:10843666.
21. 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;23:549-55; PMID:12401408; http://dx.doi.org/10.1016/S1471-4906(02)02302-5.
22. Clark WH Jr., Elder DE, Guerry D 4th, Braitman LE, Trock BJ, Schultz D, et al. Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst 1989; 81:1893-904; PMID:2593166; http://dx.doi.org/10.1093/jnci/81.24.1893.
23. Klintrup K, Mäkinen JM, Kauppila S, Väre PO, Melkko J, Tuominen H, et al. Inflammation and prognosis in colorectal cancer. Eur J Cancer 2005; 41:2645-54; PMID:16239109; http://dx.doi.org/10.1016/j.ejca.2005.07.017.
24. Cai T, Nesi G, Boddi V, Mazzoli S, Dal Canto M, Bartoletti R. Prognostic role of the tumor-associated tissue inflammatory reaction in transitional bladder cell carcinoma. Oncol Rep 2006; 16:329-34; PMID:16820911.
25. Lee AH, Gillett CE, Ryder K, Fentiman IS, Miles DW, Millis RR. Different patterns of inflammation and prognosis in invasive carcinoma of the breast. Histopathology 2006; 48:692-701; PMID:16681685; http://dx.doi.org/10.1111/j.1365-2559.2006.02410.x.
26. Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 2003; 348:203-13; PMID:12529460; http://dx.doi.org/10.1056/NEJMoa020177.
27. Cho Y, Miyamoto M, Kato K, Fukunaga A, Shichinohe T, Kawarada Y, et al. CD4+ and CD8+ T cells cooperate to improve prognosis of patients with esophageal squamous cell carcinoma. Cancer Res 2003; 63:1555-9; PMID:12670904.
28. Yoshida N, Abe H, Ohkuri T, Wakita D, Sato M, Noguchi D, et al. Expression of the MAGE-A4 and NY-ESO-1 cancer-testis antigens and T cell infiltration in non-small cell lung carcinoma and their prognostic significance. Int J Oncol 2006; 28:1089-98; PMID:16596224.
29. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pagès C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006; 313:1960-4; PMID:17008531; http://dx.doi.org/10.1126/science.1129139.
30. Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH, et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol 2011; 29:1949-55; PMID:21483002; http://dx.doi.org/10.1200/JCO.2010.30.5037.
31. Kohrt HE, Nouri N, Nowels K, Johnson D, Holmes S, Lee PP. Profile of immune cells in axillary lymph nodes predicts disease-free survival in breast cancer. PLoS Med 2005; 2:e284; PMID:16124834; http://dx.doi.org/10.1371/journal.pmed.0020284.
32. Budhu A, Forgues M, Ye QH, Jia HL, He P, Zanetti KA, et al. Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell 2006; 10:99-111; PMID:16904609; http://dx.doi.org/10.1016/j.ccr.2006.06.016.
33. Kristensen VN, Vaske CJ, Ursini-Siegel J, Van Loo P, Nordgard SH, Sachidanandam R, et al. Integrated molecular profiles of invasive breast tumors and ductal carcinoma in situ (DCIS) reveal differential vascular and interleukin signaling. Proc Natl Acad Sci USA 2012; 109:2802-7; PMID:21908711; http://dx.doi.org/10.1073/pnas.1108781108.
34. Shimura S, Yang G, Ebara S, Wheeler TM, Frolov A, Thompson TC. Reduced infiltration of tumorassociated macrophages in human prostate cancer: association with cancer progression. Cancer Res 2000; 60:5857-61; PMID:11059783.
35. Welsh TJ, Green RH, Richardson D, Waller DA, O'Byrne KJ, Bradding P. Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer. J Clin Oncol 2005; 23:8959/cimm; PMID:16219934; http://dx.doi.org/10.1200/JCO.2005.01.4910.
36. Forssell J, Oberg A, Henriksson ML, Stenling R, Jung A, Palmqvist R. High macrophage infiltration along the tumor front correlates with improved survival in colon cancer. Clin Cancer Res 2007; 13:1472-9; PMID:17332291; http://dx.doi.org/10.1158/1078-0432.CCR-06-2073.
37. Ben Aribia MH, Leroy E, Lantz O, Métivier D, Autran B, Charpentier B, et al. rIL 2-induced proliferation of human circulating NK cells and T lymphocytes: synergistic effects of IL 1 and IL 2. J Immunol 1987; 139:443-51; PMID:3110271.
38. Von Stebut E, Ehrchen JM, Belkaid Y, Kostka SL, Molle K, Knop J, et al. Interleukin 1alpha promotes Th1 differentiation and inhibits disease progression in Leishmania major-susceptible BALB/c mice. J Exp Med 2003; 198:191-9; PMID:12860932; http://dx.doi.org/10.1084/jem.20030159.
39. Ben-Sasson SZ, Hu-Li J, Quiel J, Cauchetaux S, Ratner M, Shapira I, et al. IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation. Proc Natl Acad Sci USA 2009; 106:7119-24; PMID:19359475; http://dx.doi.org/10.1073/pnas.0902745106.
40. Lipsky PE, Thompson PA, Rosenwasser LJ, Dinarello CA. The role of interleukin 1 in human B cell activation: inhibition of B cell proliferation and the generation of immunoglobulin-secreting cells by an antibody against human leukocytic pyrogen. J Immunol 1983; 130:2708-14; PMID:6222114.
41. Dustin ML, Rothlein R, Bhan AK, Dinarello CA, Springer TA. Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol 1986; 137:245-54; PMID:3086451.
42. Bani MR, Garofalo A, Scanziani E, Giavazzi R. Effect of interleukin-1-beta on metastasis formation in different tumor systems. J Natl Cancer Inst 1991; 83:119-23; PMID:1988686; http://dx.doi.org/10.1093/jnci/83.2.119.
43. Voronov E, Shouval DS, Krelin Y, Cagnano E, Benharroch D, Iwakura Y, et al. IL-1 is required for tumor invasiveness and angiogenesis. Proc Natl Acad Sci USA 2003; 100:2645-50; PMID:12598651; http://dx.doi.org/10.1073/pnas.0437939100.
44. Onozaki K, Matsushima K, Aggarwal BB, Oppenheim JJ. Human interleukin 1 is a cytocidal factor for several tumor cell lines. J Immunol 1985; 135:3962-8; PMID:2415593.
45. Philip R, Epstein LB. Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, gamma-interferon and interleukin-1. Nature 1986; 323:86-9; PMID:3092113; http://dx.doi.org/10.1038/323086a0.
46. Nakamura S, Nakata K, Kashimoto S, Yoshida H, Yamada M. Antitumor effect of recombinant human interleukin 1 alpha against murine syngeneic tumors. Jpn J Cancer Res 1986; 77:767-73; PMID:3093425.
47. North RJ, Neubauer RH, Huang JJ, Newton RC, Loveless SE. Interleukin 1-induced, T cell-mediated regression of immunogenic murine tumors. Requirement for an adequate level of already acquired host concomitant immunity. J Exp Med 1988; 168:2031-43; PMID:3143799; http://dx.doi.org/10.1084/jem.168.6.2031.
48. Voronov E, Weinstein Y, Benharroch D, Cagnano E, Ofir R, Dobkin M, et al. Antitumor and immunotherapeutic effects of activated invasive T lymphoma cells that display short-term interleukin 1alpha expression. Cancer Res 1999; 59:1029-35; PMID:10070959.
49. Song X, Voronov E, Dvorkin T, Fima E, Cagnano E, Benharroch D, et al. Differential effects of IL-1 alpha and IL-1 beta on tumorigenicity patterns and invasiveness. J Immunol 2003; 171:6448-56; PMID:14662844.
50. Allen IC, TeKippe EM, Woodford RM, Uronis JM, Holl EK, Rogers AB, et al. The NLRP3 inflammasome functions as a negative regulator of tumorigenesis during colitis-associated cancer. J Exp Med 2010; 207:1045-56; PMID:20385749; http://dx.doi.org/10.1084/jem.20100050.
51. Ghiringhelli F, Apetoh L, Tesniere A, Aymeric L, Ma Y, Ortiz C, et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med 2009; 15:1170-8; PMID:19767732; http://dx.doi.org/10.1038/nm.2028.
52. Vangsted AJ, Klausen TW, Abildgaard N, Andersen NF, Gimsing P, Gregersen H, et al. Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib. Ann Hematol 2011; 90:1173-81; PMID:21347685; http://dx.doi.org/10.1007/s00277-011-1194-3.
53. Koide SL, Inaba K, Steinman RM. Interleukin 1 enhances T-dependent immune responses by amplifying the function of dendritic cells. J Exp Med 1987; 165:515-30; PMID:2950198; http://dx.doi.org/10.1084/jem.165.2.515.
54. Pape KA, Khoruts A, Mondino A, Jenkins MK. Inflammatory cytokines enhance the in vivo clonal expansion and differentiation of antigen-activated CD4+ T cells. J Immunol 1997; 159:591-8; PMID:9218573.
55. McCune CS, Marquis DM. Interleukin 1 as an adjuvant for active specific immunotherapy in a murine tumor model. Cancer Res 1990; 50:1212-5; PMID:2297770.
56. Moriguchi Y, Kan N, Okino T, Harada T, Yamasaki S, Ichinose Y, et al. A new model of active specific immunotherapy using interleukin-1 and sonicated tumor supernatant in murine tumor system. J Surg Oncol 1996; 62:78-85; PMID:8649045; http://dx.doi.org/10.1002/(SICI)1096-9098(199606)62:2<78::AIDJSO2>3.0.CO;2-N.
57. Hakim I, Levy S, Levy R. A nine-amino acid peptide from IL-1beta augments antitumor immune responses induced by protein and DNA vaccines. J Immunol 1996; 157:5503-11; PMID:8955200.
58. Kopf M, Baumann H, Freer G, Freudenberg M, Lamers M, Kishimoto T, et al. Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 1994; 368:339-42; PMID:8127368; http://dx.doi.org/10.1038/368339a0.
59. Mulé JJ, McIntosh JK, Jablons DM, Rosenberg SA. Antitumor activity of recombinant interleukin 6 in mice. J Exp Med 1990; 171:629-36; PMID:2307930; http://dx.doi.org/10.1084/jem.171.3.629. 60. Mulé JJ, Custer MC, Travis WD, Rosenberg SA. Cellular mechanisms of the antitumor activity of recombinant IL-6 in mice. J Immunol 1992; 148:2622-9; PMID:1348521.
60. Mulé JJ, Custer MC, Travis WD, Rosenberg SA. Cellular mechanisms of the antitumor activity of recombinant IL-6 in mice. J Immunol 1992; 148:2622-9; PMID:1348521
61. Givon T, Slavin S, Haran-Ghera N, Michalevicz R, Revel M. Antitumor effects of human recombinant interleukin-6 on acute myeloid leukemia in mice and in cell cultures. Blood 1992; 79:2392-8; PMID:1571551.
62. Sun WH, Kreisle RA, Phillips AW, Ershler WB. In vivo and in vitro characteristics of interleukin 6-transfected B16 melanoma cells. Cancer Res 1992; 52:5412-5; PMID:1394147
63. Porgador A, Tzehoval E, Katz A, Vadai E, Revel M, Feldman M, et al. Interleukin 6 gene transfection into Lewis lung carcinoma tumor cells suppresses the malignant phenotype and confers immunotherapeutic competence against parental metastatic cells. Cancer Res 1992; 52:3679-86; PMID:1617640.
64. Mullen CA, Coale MM, Levy AT, Stetler-Stevenson WG, Liotta LA, Brandt S, et al. Fibrosarcoma cells transduced with the IL-6 gene exhibited reduced tumorigenicity, increased immunogenicity, and decreased metastatic potential. Cancer Res 1992; 52:6020-4; PMID:1394227.
65. Graf MR, Merchant RE. Interleukin-6 transduction of a rat T9 glioma clone results in attenuated tumorigenicity and induces glioma immunity in Fischer F344 rats. J Neurooncol 1999; 45:209-18; PMID:10845391; http://dx.doi.org/10.1023/A:1006357424124.
66. Oldford SA, Haidl ID, Howatt MA, Leiva CA, Johnston B, Marshall JS. A critical role for mast cells and mast cell-derived IL-6 in TLR2-mediated inhibition of tumor growth. J Immunol 2010; 185:7067-76; PMID:21041732; http://dx.doi.org/10.4049/jimmunol.1001137.
67. Fisher DT, Chen Q, Skitzki JJ, Muhitch JB, Zhou L, Appenheimer MM, et al. IL-6 trans-signaling licenses mouse and human tumor microvascular gateways for trafficking of cytotoxic T cells. J Clin Invest 2011; 121:3846-59; PMID:21926464; http://dx.doi.org/10.1172/JCI44952.
68. Aderka D, Maor Y, Novick D, Engelmann H, Kahn Y, Levo Y, et al. Interleukin-6 inhibits the proliferation of B-chronic lymphocytic leukemia cells that is induced by tumor necrosis factor-alpha or -beta. Blood 1993; 81:2076-84; PMID:8386026.
69. Lu C, Vickers MF, Kerbel RS. Interleukin 6: a fibroblast-derived growth inhibitor of human melanoma cells from early but not advanced stages of tumor progression. Proc Natl Acad Sci USA 1992; 89:9215-9; PMID:1409627; http://dx.doi.org/10.1073/pnas.89.19.9215.
70. Chen G, Goeddel DV. TNF-R1 signaling: a beautiful pathway. Science 2002; 296:1634-5; PMID:12040173; http://dx.doi.org/10.1126/science.1071924.
71. Chatzidakis I, Mamalaki C. T cells as sources and targets of TNF: implications for immunity and autoimmunity. Curr Dir Autoimmun 2010; 11:105-18; PMID:20173390; http://dx.doi.org/10.1159/000289200.
72. Balkwill F. Tumour necrosis factor and cancer. Nat Rev Cancer 2009; 9:361-71; PMID:19343034; http://dx.doi.org/10.1038/nrc2628.
73. Moore RJ, Owens DM, Stamp G, Arnott C, Burke F, East N, et al. Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis. Nat Med 1999; 5:828-31; PMID:10395330; http://dx.doi.org/10.1038/10552.
74. Ferrajoli A, Keating MJ, Manshouri T, Giles FJ, Dey A, Estrov Z, et al. The clinical significance of tumor necrosis factor-alpha plasma level in patients having chronic lymphocytic leukemia. Blood 2002; 100:1215-9; PMID:12149200.
75. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 1975; 72:3666-70; PMID:1103152; http://dx.doi.org/10.1073/pnas.72.9.3666.
76. Havell EA, Fiers W, North RJ. The antitumor function of tumor necrosis factor (TNF), I. Therapeutic action of TNF against an established murine sarcoma is indirect, immunologically dependent, and limited by severe toxicity. J Exp Med 1988; 167:1067-85; PMID:3351434; http://dx.doi.org/10.1084/jem.167.3.1067.
77. Helson L, Green S, Carswell E, Old LJ. Effect of tumour necrosis factor on cultured human melanoma cells. Nature 1975; 258:731-2; PMID:1207755; http://dx.doi.org/10.1038/258731a0.
78. Fransen L, Van der Heyden J, Ruysschaert R, Fiers W. Recombinant tumor necrosis factor: its effect and its synergism with interferon-gamma on a variety of normal and transformed human cell lines. Eur J Cancer Clin Oncol 1986; 22:419-26; PMID:3089802; http://dx.doi.org/10.1016/0277-5379(86)90107-0.
79. McIntosh JK, Mulé JJ, Merino MJ, Rosenberg SA. Synergistic antitumor effects of immunotherapy with recombinant interleukin-2 and recombinant tumor necrosis factor-alpha. Cancer Res 1988; 48:4011-7; PMID:3260130.
80. Blankenstein T, Qin ZH, Uberla K, Müller W, Rosen H, Volk HD, et al. Tumor suppression after tumor cell-targeted tumor necrosis factor alpha gene transfer. J Exp Med 1991; 173:1047-52; PMID:2022919; http://dx.doi.org/10.1084/jem.173.5.1047.
81. Hock H, Dorsch M, Kunzendorf U, Qin Z, Diamantstein T, Blankenstein T. Mechanisms of rejection induced by tumor cell-targeted gene transfer of interleukin 2, interleukin 4, interleukin 7, tumor necrosis factor, or interferon gamma. Proc Natl Acad Sci USA 1993; 90:2774-8; PMID:8464888; http://dx.doi.org/10.1073/pnas.90.7.2774.
82. Qin Z, Krüger-Krasagakes S, Kunzendorf U, Hock H, Diamantstein T, Blankenstein T. Expression of tumor necrosis factor by different tumor cell lines results either in tumor suppression or augmented metastasis. J Exp Med 1993; 178:355-60; PMID:8315391; http://dx.doi.org/10.1084/jem.178.1.355.
83. Smyth MJ, Kelly JM, Baxter AG, Körner H, Sedgwick JD. An essential role for tumor necrosis factor in natural killer cell-mediated tumor rejection in the peritoneum. J Exp Med 1998; 188:1611-9; PMID:9802973; http://dx.doi.org/10.1084/jem.188.9.1611.
84. Swann JB, Vesely MD, Silva A, Sharkey J, Akira S, Schreiber RD, et al. Demonstration of inflammation-induced cancer and cancer immunoediting during primary tumorigenesis. Proc Natl Acad Sci USA 2008; 105:652-6; PMID:18178624; http://dx.doi.org/10.1073/pnas.0708594105.
85. Calzascia T, Pellegrini M, Hall H, Sabbagh L, Ono N, Elford AR, et al. TNF-alpha is critical for antitumor but not antiviral T cell immunity in mice. J Clin Invest 2007; 117:3833-45; PMID:17992258.
86. Lejeune FJ, Liénard D, Matter M, Rüegg C. Efficiency of recombinant human TNF in human cancer therapy. Cancer Immun 2006; 6:6; PMID:16551058.
87. Lienard D, Ewalenko P, Delmotte JJ, Renard N, Lejeune FJ. High-dose recombinant tumor necrosis factor alpha in combination with interferon gamma and melphalan in isolation perfusion of the limbs for melanoma and sarcoma. J Clin Oncol 1992; 10:52-60; PMID:1727926.
88. Eggermont AM, Schraffordt Koops H, Klausner JM, Kroon BB, Schlag PM, Liénard D, et al. Isolated limb perfusion with tumor necrosis factor and melphalan for limb salvage in 186 patients with locally advanced soft tissue extremity sarcomas. The cumulative multicenter European experience. Ann Surg 1996; 224:756-64, discussion 764-5; PMID:8968230; http://dx.doi.org/10.1097/00000658-199612000-00011.
89. Santoro A, Pressiani T, Citterio G, Rossoni G, Donadoni G, Pozzi F, et al. Activity and safety of NGRhTNF, a selective vascular-targeting agent, in previously treated patients with advanced hepatocellular carcinoma. Br J Cancer 2010; 103:837-44; PMID:20717115; http://dx.doi.org/10.1038/sj.bjc.6605858.
90. Jung M, Dimtchev A, Velena A, Dritschilo A. Combining radiation therapy with interstitial radiation-inducible TNF-a expression for locoregional cancer treatment. Cancer Gene Ther 2011; 18:189-95; PMID:21052099; http://dx.doi.org/10.1038/cgt.2010.69.
91. Johansson A, Hamzah J, Payne CJ, Ganss R. Tumortargeted TNFa stabilizes tumor vessels and enhances active immunotherapy. Proc Natl Acad Sci USA 2012; 109:7841-6; PMID:22547817; http://dx.doi.org/10.1073/pnas.1118296109.
92. Talmadge JE, Tribble HR, Pennington RW, Phillips H, Wiltrout RH. Immunomodulatory and immunotherapeutic properties of recombinant gamma-interferon and recombinant tumor necrosis factor in mice. Cancer Res 1987; 47:2563-70; PMID:3105865.
93. Belardelli F, Ciolli V, Testa U, Montesoro E, Bulgarini D, Proietti E, et al. Anti-tumor effects of interleukin-2 and interleukin-1 in mice transplanted with different syngeneic tumors. Int J Cancer 1989; 44:1108-16; PMID:2606579; http://dx.doi.org/10.1002/ijc.2910440629.
94. Vercammen E, Staal J, Van Den Broeke A, Haegman M, Vereecke L, Schotte P, et al. Prolonged exposure to IL-1beta and IFNgamma induces necrosis of L929 tumor cells via a p38MAPK/NF-kappaB/ NO-dependent mechanism. Oncogene 2008; 27:3780-8; PMID:18246123; http://dx.doi.org/10.1038/onc.2008.4.
95. Yip I, Pang XP, Berg L, Hershman JM. Antitumor actions of interferon-gamma and interleukin-1 beta on human papillary thyroid carcinoma cell lines. J Clin Endocrinol Metab 1995; 80:1664-9; PMID:7745015; http://dx.doi.org/10.1210/jc.80.5.1664.
96. Hori K, Ehrke MJ, Mace K, Mihich E. Effect of recombinant tumor necrosis factor on tumoricidal activation of murine macrophages: synergism between tumor necrosis factor and gamma-interferon. Cancer Res 1987; 47:5868-74; PMID:3117358.
97. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 1986; 136:2348-57; PMID:2419430.
98. Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, et al. Demonstration of an interferon gamma-dependent tumor surveillance system in immunocompetent mice. Proc Natl Acad Sci USA 1998; 95:7556-61; PMID:9636188; http://dx.doi.org/10.1073/pnas.95.13.7556.
99. Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, et al. IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 2001; 410:1107-11; PMID:11323675; http://dx.doi.org/10.1038/35074122.
100. Schreiber RD, Pace JL, Russell SW, Altman A, Katz DH. Macrophage-activating factor produced by a T cell hybridoma: physiochemical and biosynthetic resemblance to gamma-interferon. J Immunol 1983; 131:826-32; PMID:6408190.
101. Pace JL, Russell SW, Schreiber RD, Altman A, Katz DH. Macrophage activation: priming activity from a T-cell hybridoma is attributable to interferon-gamma. Proc Natl Acad Sci USA 1983; 80:3782-6; PMID:6407020; http://dx.doi.org/10.1073/pnas.80.12.3782.
102. Schultz RM, Kleinschmidt WJ. Functional identity between murine gamma interferon and macrophage activating factor. Nature 1983; 305:239-40; PMID:6412144; http://dx.doi.org/10.1038/305239a0.
103. Sgadari C, Angiolillo AL, Cherney BW, Pike SE, Farber JM, Koniaris LG, et al. Interferon-inducible protein-10 identified as a mediator of tumor necrosis in vivo. Proc Natl Acad Sci USA 1996; 93:13791-6; PMID:8943014; http://dx.doi.org/10.1073/pnas.93.24.13791.
104. Arenberg DA, Kunkel SL, Polverini PJ, Morris SB, Burdick MD, Glass MC, et al. Interferon-gammainducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases. J Exp Med 1996; 184:981-92; PMID:9064358; http://dx.doi.org/10.1084/jem.184.3.981.
105. Sgadari C, Farber JM, Angiolillo AL, Liao F, Teruya-Feldstein J, Burd PR, et al. Mig, the monokine induced by interferon-gamma, promotes tumor necrosis in vivo. Blood 1997; 89:2635-43; PMID:9108380.
106. Bonecchi R, Bianchi G, Bordignon PP, D'Ambrosio D, Lang R, Borsatti A, et al. Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med 1998; 187:129-34; PMID:9419219; http://dx.doi.org/10.1084/jem.187.1.129.
107. Nakanishi Y, Lu B, Gerard C, Iwasaki A. CD8(+) T lymphocyte mobilization to virus-infected tissue requires CD4(+) T-cell help. Nature 2009; 462:510-3; PMID:19898495; http://dx.doi.org/10.1038/nature08511.
108. Parr I, Wheeler E, Alexander P. Similarities of the anti-tumour actions of endotoxin, lipid A and double-stranded RNA. Br J Cancer 1973; 27:370-89; PMID:4713170; http://dx.doi.org/10.1038/bjc.1973.45.
109. Vicari AP, Chiodoni C, Vaure C, Aït-Yahia S, Dercamp C, Matsos F, et al. Reversal of tumor-induced dendritic cell paralysis by CpG immunostimulatory oligonucleotide and anti-interleukin 10 receptor antibody. J Exp Med 2002; 196:541-9; PMID:12186845; http://dx.doi.org/10.1084/jem.20020732.
110. Alexandroff AB, Nicholson S, Patel PM, Jackson AM. Recent advances in bacillus Calmette-Guerin immunotherapy in bladder cancer. Immunotherapy 2010; 2:551-60; PMID:20636008; http://dx.doi.org/10.2217/imt.10.32.
111. Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, et al. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 2002; 3:196-200; PMID:11812998; http://dx.doi.org/10.1038/ni758.
112. Geisse JK, Rich P, Pandya A, Gross K, Andres K, Ginkel A, et al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: a doubleblind, randomized, vehicle-controlled study. J Am Acad Dermatol 2002; 47:390-8; PMID:12196749; http://dx.doi.org/10.1067/mjd.2002.126215.
113. Lebwohl M, Dinehart S, Whiting D, Lee PK, Tawfik N, Jorizzo J, et al. Imiquimod 5% cream for the treatment of actinic keratosis: results from two phase III, randomized, double-blind, parallel group, vehiclecontrolled trials. J Am Acad Dermatol 2004; 50:714-21; PMID:15097955; http://dx.doi.org/10.1016/j.jaad.2003.12.010.
114. van Seters M, van Beurden M, ten Kate FJ, Beckmann I, Ewing PC, Eijkemans MJ, et al. Treatment of vulvar intraepithelial neoplasia with topical imiquimod. N Engl J Med 2008; 358:1465-73; PMID:18385498; http://dx.doi.org/10.1056/NEJMoa072685.
115. Nowak AK, Lake RA, Marzo AL, Scott B, Heath WR, Collins EJ, et al. Induction of tumor cell apoptosis in vivo increases tumor antigen cross-presentation, cross-priming rather than cross-tolerizing host tumorspecific CD8 T cells. J Immunol 2003; 170:4905-13; PMID:12734333.
116. Nowak AK, Robinson BW, Lake RA. Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors. Cancer Res 2003; 63:4490-6; PMID:12907622.
117. Nisticò P, Capone I, Palermo B, Del Bello D, Ferraresi V, Moschella F, et al. Chemotherapy enhances vaccineinduced antitumor immunity in melanoma patients. Int J Cancer 2009; 124:130-9; PMID:18839429; http://dx.doi.org/10.1002/ijc.23886.
118. Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 2007; 13:1050-9; PMID:17704786; http://dx.doi.org/10.1038/nm1622.