Regulation of NK cell activation by stimulatory and inhibitory receptors in tumor escape from innate immunity

Frontiers in Bioscience

Volumn 10, Issue SUPPL. 3, 2005, Pages 3132-3142

  Wu, Peng ^a   Wei, Haiming ^a   Zhang, Cai ^c   Zhang, Jian ^b   Tian, Zhigang ^a,b,c  

^a UNIVERSITY OF SCIENCE AND TECHNOLOGY OF CHINA   (China)

^b SHANDONG UNIVERSITY   (China)

^c SHANDONG PROVINCIAL HOSPITAL AFFILIATED TO SHANDONG FIRST MEDICAL UNIVERSITY   (China)

Author keywords

Cellular stress; Heat shock protein; Immunosurveillance; NCRs; NK cells; NKG2D; Review; Stimulatory immunoreceptors; Tumor

Indexed keywords

GLYCOLIPID; GLYCOPROTEIN; HEAT SHOCK PROTEIN; OLIGOSACCHARIDE;

CELL ACTIVATION; CELL INTERACTION; CELL STIMULATION; CELLULAR IMMUNITY; IMMUNOSURVEILLANCE; INNATE IMMUNITY; NATURAL KILLER CELL; NONHUMAN; REVIEW; TARGET CELL; TUMOR IMMUNITY;

EID: 21344471948     PISSN: 27686701     EISSN: 27686698     Source Type: Journal    
DOI: 10.2741/1770     Document Type: Review

References (101)

1. Trinchieri G.: Biology of natural killer cells. Adv Immunol 47, 187-376 (1989)
2. French A.R. & Yokoyama W.M.: Natural killer cells and viral infections. Curr Opin Immunol 15, 45-51 (2003)
3. Smyth M.J., Godfrey D.I. & Trapani J.A.: A fresh look at tumor immunosurveillance and immunotherapy. Nat Immunol 2, 293-299 (2001)
4. Biron C.A.: Activation and function of natural killer cell responses during viral infections. Curr Opin Immunol 9, 24-34 (1997)
5. Biron C.A., Nguyen K.B., Pien G.C., Cousens L.P. & Salazar-Mather T.P.: Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 17, 189-220 (1999)
6. Karlhofer F.M., Ribaudo R.K. & Yokoyama W.M.: MHC class I alloantigen specificity of Ly-49+ IL-2 activated natural killer cells. Nature 358, 66-70 (1992)
7. Colonna M. & Samaridis J.: Cloning of immunoglobulin-superfamily members associated with HLA-C and HLA-B recognition by human natural killer cells. Science 268, 405-408 (1995)
8. Wagtmann N., Biassoni R., Cantoni C., Verdiani S., Malnati M.S., Vitale M., Bottino C., Moretta L., Moretta A. & Long E.O.: Molecular clones of the p58 natural killer cell receptor reveal Ig-related molecules with diversity in both the extra- and intra-cellular domains. Immunity 2, 439-449 (1995)
9. Cosman D., Neil F., Luis B., Marek K., Wilson C., Lori P. & Mei-Ling Hsu: A novel immunoglobulin superfamily receptor for cellular and viral MHC class I molecules. Immunity 1, 273-282 (1997)
10. Samaridis J. & Colonna M.: Cloning of novel immunoglobulin superfamily receptors expressed on human myeloid and lymphoid cells: structural evidence for new stimulatory and inhibitory pathways. Eur J Immuno 27, 660-665 (1997)
11. Braud V.M., Allan D.S., O'Callaghan C.A., Soderstrom K., D'Andrea A, Ogg O.S., Lazetic S., Young N.T., Bell J.I., Phillips J.H., Lanier L.L. & McMichael A.J.: HLA-E binds to natural killer cell receptors CD94/NKG2A, B, and C. Nature 391, 795-799 (1998)
12. Lee N., Llano M., Carretero M., Ishitani A., Navarro F., Lopez-Botet M. & Geraghty D.E.: HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A. Proc Natl Acad Sci USA 95, 5199-5204 (1998)
13. Vance R.E., Kraft J.R., Altman J.D., Jensen P.E. & Raulet D.H.: Mouse CD94/NKG2A is a natural killer cell receptor for the nonclassical MHC class I molecule Qa-1b. J Exp Med 188, 1841-1848 (1998)
14. Lanier L.L.: NK cell receptors. Annu Rev Immunol 16, 359-393 (1998)
15. Moretta L., Biassoni R., Bottino C., Mingari C.& Moretta A.: Natural Killer cells: A mystery no more. Scand J Immunol 55, 229-232 (2002)
16. Kärre K.: NK cells, MHC class I molecules and the missing self. Scand J Immunol 55, 221-228 (2002)
17. Moretta A., Bottino R. & Vitale M.: Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19, 197-223 (2001)
18. Bruce Beutler: Innate immunity: an overview. Molecular Immunology 40, 845-859 (2004)
19. Ljunggren H.G. & Kärre K.: Host resistance directed selectively against H-2-deficient lymphoma variants. J Exp Med 162, 1745-1759 (1985)
20. Bix M., Liao N.S., Zijlstra M., Loring J., Jaenisch R. & Raulet D.: Rejection of class I MHC-deficient hemopoietic cells by irradiated MHC-matched mice. Nature 349, 329-331 (1991)
21. Rault D.H.: Roles of the NKG2D immunoreceptor and its ligands. Nat Rev Immunol 3, 781-790 (2003)
22. Cerwenka A. & Lanier L.L.: NKG2D ligands: unconventional MHC class I-like molecules exploited by viruses and cancer. Tissue antigens 61, 335-343 (2003)
23. Raulet D.H.: Interplay of natural killer cells and their receptors with the adaptive immune response. Nat Immunol 5, 996-1002 (2004)
24. Gleimer M. & Parham P.: Stress management: MHC class I and Class I-like molecules as reporters of cellular stress. Immunity 19, 469-477 (2003)
25. Bauer S., Groh V., Wu J., Steinle A., Phillips J.H., Lanier L.L., & Spies T.: Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 285, 727-729 (1999)
26. Wu J., Song Y., Bakker A.B., Bauer S., Spies T., Lanier L.L. & Phillips J.H.: An activating immunoreceptor complex formed by NKG2D and DAP10. Science 285, 730-732 (1999)
27. Groh V., Rhinehart R., Randolph-Habecker J., Topp M.S., Riddell S.R. & Spies T.: Costimulation of CDS alphabeta T cells by NKG2D via engagement by MIC induced on virus-infected cells. Nat Immunol 2, 255-260 (2001)
28. Das H., Groh V., Kuijl C., Sugita M., Morita C.T., Spies T. & Bukowski J.F.: MICA engagement by human V gamma2 Vdelta2 T cells enhances their antigen-dependent effector function. Immunity 15, 83-93 (2001)
29. Diefenbach A., Jamieson A.M., Liu S.D., Shastri N. & Raulet D.H.: Ligands for the murine NKG2D receptor: expression by tumor cells and activation of NK cells and macrophages. Nat Immunol 1, 119-120 (2000)
30. Diefenbach A., Jensen E.R., Jamieson A.M. & Raulet D.H.: Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature 413, 165-171 (2001)
31. Cosman D., Mullberg J., Sutherland C.L., Chin W. & Armitage R.: ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity 14, 123-133 (2001)
32. Jamieson A.M., Diefenbach A., McMahon C.W., Xiong N., Carlyle J.R. & Raulet D.H.: The role of the NKG2D immunoreceptor in immune cell activation and natural killing. Immunity 17, 19-29 (2002)
33. Kubin M., Cassiano L., Chalupny J., Chin W., Cosman D., Fanslow W., Mullberg J., Roussaau A.M., Ulrich D. & Armitage R.: ULBP 1,2,3: novel MHC class I-related molecules that binds to human cytomegalovirus glycoprotein UL16, activate NK cells. Eur J Immunol 31, 1428-1437 (2001)
34. Sutherland C.L., Chalupny N.J., Schooley K., VandenBos T., Kubin M. & Cosman D.: UL16-binding proteins, novel MHC class I-related proteins, bind to NKG2D and activate multiple signaling pathways in primary NK cells. J Immunol 168, 671-679 (2002)
35. Veronika G., Rebecca R., Heather S., Stefan B., Kenneth H.G. & Thomas S.: Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB. Proc Natl Acad Sci USA 96, 6879-6884 (1999)
36. Lodoen M., Ogasawara K., Hamerman J.A., Arase H., Houchins J.P., Mocarski E.S. & Lanier L.L.: NKG2D-mediated natural killer cell protection against cytomegalovirus is impaired by viral gp40 modulation of retinoic acid early inducible 1 gene molecules. J Exp Med 197, 1245-1253 (2003)
37. Bahram S., Bresnahan M., Geraghty D.E. & Speies T.: A second lineage of mammalian major histocompatibility complex class I genes. Proc Natl Acad Sci USA 91, 6159-6263 (1994)
38. Groh V., Bahram S., Bauer S., Herman A., Beauchamp M. & Spies T.: Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium. Proc Natl Acad Sci USA 93, 12445-12450 (1996)
39. Tieng V., Le Bouguenec C., du Merle L., Bertheau P., Desreumaux P., Janin A., Charron D. & Toubert A.: Binding of Escherichia coli adhesin AfaE to CD55 triggers cell-surface expression of the MHC class Irelated molecule MICA. Proc Natl Acad Sci USA 99, 2977-2982 (2002)
40. Jinushi M., Takehara T., Tatsumi T., Kanto T., Groh V., Spies T., Kimura R., Miyagi T., Mochizuki K., Sasaki Y. & Hayashi N.: Expression and role of MICA and MICB in human hepatocellular carcinomas and their regulation by retinoic acid. Int J Cancer 104, 354-361 (2003)
41. Diefenbach A. & Raulet D.H.: Innate immune recognition by stimulatory immunoreceptors. Curr Opin Immunol 15, 37-44 (2003)
42. Diefenbach A., Hsia J.K., Hsiung M.Y. & Raulet D.H.: A novel ligand for the NKG2D receptor activates NK cells and macrophages and induces tumor immunity. Eur J Immunol 33, 381-391 (2003)
43. Pende D., Rivera P., Marcenaro S., Chang C.C., Biassoni R., Conte R., Kubin M., Cosman D., Ferrone S., Moretta L. & Moretta A.: Major histocompatibility complex class I related chain A and UL16-binding protein expression on tumor cell lines of different histotypes: analysis of tumor susceptibility to NKG2D-dependent natural killer cell cytotoxicity. Cancer Res 62, 6178-6186 (2002)
44. Dunn G.P., Old L.J. & Schreiber R.D.: The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21, 137-148 (2004)
45. Moretta A., Biassoni R., Bottino C., Mingari M.C. & Moretta L.: Natural cytotoxicity receptors that trigger human NK-cell-mediated cytolysis. Immunol Today 21, 228-234 (2000)
46. Biassoni R., Cantoni C., Marras D., Giron-Michel J., Falco M., Moretta L. & Dimasi N.: Human natural killer cell receptors: insights into their molecular function and structure. J Cell Mol Med 7, 376-387 (2003)
47. Sivori S., Pende D., Bottino C., Marcenaro E., Pessino A., Biassoni R., Moretta L. & Moretta A.: NKp46 is the major triggering receptor involved in the natural cytotoxicity of fresh or cultured human NK cells. Correlation between surface density of NKp46 and natural cytotoxicity against autologous, allogeneic or xenogeneic target cells. Eur J Immunol 29, 1656-1666 (1999)
48. Bloushtain N., Qimron U., Bar-Ilan A., Hershkovitz O., Gazit R., Fima E., Korc M., Vlodavsky I., Bovin N.V. & Porgador A.: Membrane-associated heparan sulfate proteoglycans are involved in the recognition of cellular targets by NKp30 and NKp46. J Immunol 173, 2392-2401 (2004)
49. Bezouska K., Yuen C.T., O'Brien J., Childs R.A., Chai W., Lawson A.M., Drbal K., Fiserova A., Pospisil M. & Feizi T.: Oligosaccharide ligands for NKR-P1 protein activate NK cells and cytotoxicity. Nature 372, 150-157 (1994)
50. Chang C.S. & Kane K.P.: Evidence for sulfate modification of H-2Dd on N-linked carbohydrate(s): possible involvement in Ly-49A interaction. J Immunol 160, 4367-4374 (1998)
51. Ohyama C., Kanto S., Kato K., Nakano O., Arai Y., Kato T., Chen S., Fukuda M.N. & Fukuda M.: Natural killer cells attack tumor cells expressing high levels of sialyl Lewis x oligosaccharides. Proc Natl Acad Sci USA 99, 13789-13794 (2002)
52. Fukuda M.: Possible roles of tumor-associated carbohydrate antigens. Cancer Res 56, 2237-2244 (1996)
53. Hakomori S.: Aberrant glycosylation in cancer cell membranes as focused on glycolipids: overview and perspectives. Cancer Res 45, 2405-2414 (1985)
54. Ohyama C., Fukushi Y., Satoh M., Saitoh S., Orikasa S., Nudelman E., Straud M. & Hakomori S.: Changes in glycolipid expression in human testicular tumor. Int J Cancer 45, 1040-1044 (1990)
55. Singhal A. & Hakomori S.: Molecular changes in carbohydrate antigens associated with cancer. Bioessays 12, 223-230 (1990)
56. Lloyd K.O.: Carbohydrate vaccines for the immunotherapy of cancer. Drug News Perspect 13, 463-470 (2000)
57. Roder J.C., Rosen A., Fenyo E.M. & Triy F.A.: Target-effector interaction in the natural killer cell system: isolation of target structures. Proc Natl Acad Sci USA 76, 1405-1409 (1979)
58. Werkmeister J.A., Pross H.F. & Roder J.C.: Modulation of K562 cells with sodium butyrate. Association of impaired NK susceptibility with sialic acid and analysis of other parameters. Int J Cancer 32, 71-78 (1983)
59. Nestel F.P., Casson P.R., Wiltrout R.H. & Kerbel R.S.: Alterations in sensitivity to nonspecific cell-mediated lysis associated with tumor progression: characterization of activated macrophage- and natural killer cell-resistant tumor variants. J Natl Cancer Inst 73, 483-491 (1984)
60. Ahrens P.B.: Role of target cell glycoproteins in sensitivity to natural killer cell lysis. J Biol Chem 268, 385-391 (1993)
61. Long E.O. & Rajagopalan S.: Stress signals activate natural killer cells. J Exp Med 196, 1399-1402 (2002)
62. Raulet D.H., Vance R.E. & McMahon C.W.: Regulation of the natural killer cell receptor repertoire. Annu Rev Immunol 19, 291-330 (2001)
63. Brooks A.G., Borrego P., Posch P.E., Patamawenu A., Scorzelli C.J., Ulbrecht M., Weiss E.H. & Coligan J.E.: Specific recognition of HLA-E, but not classical, HLA class I molecules by soluble CD94/NKG2A and NK cells. J Immunol 162, 305-313 (1999)
64. Valés-Gómez M., Reyburn H.T., Erskine R.A., López-Botet M. & Strominger J.L.: Kinetics and peptide dependency of the binding of the inhibitory NK receptor CD94/NKG2-A and the activating receptor CD94/NKG2-C to HLA-E. EMBO J 18, 4250-4260 (1999)
65. Michaëlsson J., Teixeira de Matos C., Achour A., Lanier L.L., Karre K. & Soderstrom K.: HLA-E-mediated presentation of an hsp60 signal peptide prevents natural killer (NK) cell inhibitory receptor engagement: a novel mechanism for NK cell detection of stressed cells. J Exp Med 196, 1403-1414 (2002)
66. Imani F. & Soloski M.J.: Heat shock proteins can regulate expression of the Tla region-encoded class Ib molecule Qa-1. Proc Nat Acad Sci USA 88, 10475-10479 (1991)
67. Udono H. & Srivastava P.K.: Comparison of tumor-specific immunogenicities of stress-induced proteins gp96, hsp90, and hsp70. J Immunol 152, 5398-5403 (1994)
68. Srivastava P.K., Menoret A., Basu S., Binder R.J. & McQuade K.L.: Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world. Immunity 8, 657-665 (1998)
69. Ferrarini M., Heltai S., Zocchi M.R. & Rugarli C.: Unusual expression and localization of heat-shock proteins in human tumor cells. Int J Cancer 51, 613-619 (1992)
70. Tamura Y., Tsuboi N., Sato N. & Kikuchi K.: 70 kDa heat shock cognate protein is a transformation-associated antigen and a possible target for the host's anti-tumor immunity. J Immunol 151, 5516-5524 (1993)
71. Altmeyer A., Maki R.G., Feldweg A.M., Heike M., Protopopov V.P., Masur S.K. & Srivastava P.K.: Tumor-specific cell surface expression of the -KDEL containing, endoplasmic reticular heat shock protein gp96. Int J Cancer 69, 340-349 (1996)
72. Multhoff G., Pfister K., Gehrmann M., Hantschel M., Gross C., Hafher M. & Hiddemann W.: A 14-mer Hsp70 peptide stimulates natural killer (NK) cell activity. Cell Stress & Chaperones 6, 337-344 (2001)
73. Timonen T. & Helander T.S.: Natural killer cell-target cell interactions. Cur Opin Cell Bio 9, 667-673 (1997)
74. Onda H., Ohkubo S., Shintani Y., Ogi K., Kikuchi K., Tanaka H., Yamamoto K., Tsuji I., Ishibashi Y., Yamada T., Kitada C., Suzuki N., Sawada H., Nishimura O. & Fujino M.: A novel secrested tumor antigen with a glycosylphosphatidylinositol-anchored structure ubiquitiously expressed in human cancers. Biochem Biophys Res Commun 285, 235-243 (2001)
75. Vieira A.V., Lamaze C. & Schmid S.L.: Control of EGF Receptor Signaling by Clathrin-Mediated Endocytosis. Science 274, 2086-2089 (1996)
76. Duan L., Miura Y., Dimri M., Majumder B., Dodge I.L., Reddi A.L., Ghosh A., Fernandes N., Zhou P., Mullane-Robinson K., Rao N., Donoghue S., Rogers R.A., Bowtell D., Naramura M., Gu H., Band V. & Band H.: Cbl-mediated Ubiquitinylation Is Required for Lysosomal Sorting of Epidermal Growth Factor Receptor but Is Dispensable for Endocytosis. J Biol Chem 278, 28950-28960 (2003)
77. Herbst J.J., Opresko L.K., Walsh B.J., Lauffenburger D.A. & Wiley H.S.: Regulation of postendocytic trafficking of the epidermal growth factor receptor through endosomal retention. J Biol Chem 269, 12865-12873 (1994)
78. Beguinot L., Lyall R.M., Willingham M.C. & Pastan I.: Down-regulation of the epidermal growth factor receptor in KB Cells is due to receptor internalization and subsequent degradation in lysosomes. Proc Natl Acad Sci USA 81, 2384-2388 (1984)
79. Futter C.E., Pearse A., Hewlett L.J. & Hopkins C.R.: Multivesicular endosomes containing internalized EGF-EGF receptor complexes mature and then fuse directly with lysosomes. J Cell Biol 132, 1011-1023 (1996)
80. Burke P., Schooler K. & Wiley H.S.: Regulation of epidermal growth factor receptor signaling by endocytosis and intracellular trafficking. Mol Biol Cell 12, 1897-1910 (2001)
81. Waterman H., Sabanai I., Geiger B. & Yarden Y.: Alternative intracellular routing of ErbB receptors may determine signaling potency. J Biol Chem 273, 13819-13827 (1998)
82. Arase H., Mocarski E.S., Campbell A.E., Hill A.B. & Lanier L.L.: Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science 296, 1323-1326 (2002).
83. Smith H.R., Heusel J.W., Mehta I.K., Kim S., Dorner B.G., Naidenko O.V., Iizuka K., Furukawa H., Beckman D.L., Pingel J.T., Scalzo A.A., Fremont D.H. & Yokoyama W.M.: Recognition of a virus-encoded ligand by a natural killer cell activation receptor. Proc Natl Acad Sci USA 99, 8826-8831 (2002)
84. Brown M.G., Dokun A.O., Heusel J.W., Smith H.R., Beckman D.L., Blattenberger E.A., Dubbelde C.E., Stone L.R., Scalzo A.A., & Yokoyama W.M.: Vital involvement of a natural killer cell activation receptor in resistance to viral infection. Science 292, 934-937 (2001)
85. Mandelboim O., Lieberman N., Lev M., Paul L., Arnon T.I., Bushkin Y., Davis D.M., Strominger J.L., Yewdell J.W. & Porgador A.: Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells. Nature 409, 1055-1060 (2001)
86. Groh V., Wu J., Yee C. & Spies T.: Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature 419, 734-738 (2002)
87. Salih H.R., Antropius H., Gieseke F., Lutz S.Z., Kanz L., Rammensee H.G. & Steinle A.: Functional expression and release of ligands for the activating immunoreceptor NKG2D in leukemia. Blood 102, 1389-1396 (2003)
88. Salih H.R., Rammensee H.G. & Steinle A.: Cutting edge: down-regulation of MICA on human tumors by proteolytic shedding. J Immunol 169, 4098-4102 (2002)
89. Wu J.D., Higgins L.M., Steinle A., Cosman D., Haugk K. & Plymate S.R.: Prevalent expression of the immunostimulatory MHC class I chain-related molecule is counteracted by shedding in prostate cancer. J Clin Invest 114, 560-568 (2004)
90. Ogasawara K., Hamerman J.A., Hsin H., Chikuma S., Bour-Jordan H., Chen T., Pertel T., Carnaud C., Bluestone J.A., Lanier L.L.: Impairment of NK cell function by NKG2D modulation in NOD mice. Immunity 18, 41-51 (2003)
91. Doubrovina E.S., Doubrovin M.M., Vider E., Sisson R.B., O'Reilly R.J., Dupont B. & Vyas Y.M.: Evasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma. J Immunol 171, 6891-6899 (2003)
92. Roberts A.I., Lee L., Schwarz E., Groh V., Spies T., Ebert E.G. & Jabri B.: NKG2D receptors induced by IL-15 costimulate CD28-negative effector CTL in the tissue microvironment. J Immunol 167, 5527-5530 (2001)
93. Smyth M.J., Hayakawa Y., Takeda K. & Yagita H.: New aspects of natural-killer-cell surveillance and therapy of cancer. Nature Rev Cancer 2, 850-861 (2002)
94. Flodstrom M., Shi F.D., Sarvetnick N. & Ljunggren H.G.: The natural killer cell - friend or foe in autoimmune disease? Scand J Immunol 55, 432-441 (2002)
95. Zhang C., Zhang J., Sun R., Feng J., Wei H. & Tian Z.: opposing effect of IFN-gamma on expression of NKG2 receptors: Negative regulation of IFN-gamma on NK cells. Int Immunopharmacol 5, 1957-1067 (2005)
96. Malmberg K.J., Levitsky V., Norell H., de Matos C.T., Carlsten M., Schedvins K., Rabbani H., Moretta A., Soderstrom K., Levitskaya J. & Kiessling R.: IFN-gamma protects short-term ovarian carcinoma cell lines from CTL lysis via a CD94/NKG2A-dependent mechanism. J Clin Invest 110, 1515-1523 (2002)
97. Ross M.E. & Caligiuri M.A.: Cytokine-induced apoptosis of human NK cells identifies a novel mechanism to regulate the innate immune response. Blood 89, 910-918 (1997)
98. Freedman R.S., Kudelka A.P., Kavanagh J.J., Verschraegen C., Edwards C.L., Nash M., Levy L., Atkinson E.N., Zhang H.Z., Melichar B., Patenia R., Templin S., Scott W. & Platsoucas C.D.: Clinical and biological effects of intraperitoneal injections of recombinant interferon-gamma and recombinant interleukin 2 with or without tumor-infiltrating lymphocytes in patients with ovarian or peritoneal carcinoma. Clin Cancer Res 6, 2268-2278 (2000)
99. F.L. Meyskens Jr, Kopecky K.J., Taylor C.W., Noyes R.D., Tuthill R.J., Hersh E.M., Feun L.G., Doroshow J.H., Flaherty L.E. & Sondak V.K.: Randomized trial of adjuvant human interferon-gamma versus observation in high-risk cutaneous melanoma: a Southwest Oncology Group study. J Natl Cancer Inst 87, 1710-1713 (1995)
100. Legrand A., Vadrot N., Lardeux B., Bringuier A.F., Guillot R. & Feldmann G.: Study of the effects of interferon a on several human hepatoma cell lines: analysis of the signalling pathway of the cytokine and of its effects on apoptosis and cell proliferation. Liver Int 24, 149-160 (2004)
101. Bukowski R., Ernstoff M.S., Gore M.E., Nemunaitis J.J., Amato R., Gupta S.K. & Tendler C.L.: Pegylated interferon alfa-2b treatment for patients with solid tumors: a phase I/II study. J Clin Oncol 20, 3841-3849 (2002)