Targeting IL4/IL4R for the treatment of epithelial cancer metastasis

Clinical and Experimental Metastasis

Volumn 32, Issue 8, 2015, Pages 847-856

  Bankaitis, Katherine Venmar ^a   Fingleton, Barbara ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Cytokine; IL4; IL4 receptor; Metastasis; Proliferation; Survival

Indexed keywords

ALTRAKINCEPT; AMG 317; ANTINEOPLASTIC AGENT; CYTOKINE RECEPTOR ANTAGONIST; CYTOTOXIN; DUPILUMAB; HYBRID PROTEIN; INSULIN RECEPTOR SUBSTRATE; INTERLEUKIN 13 RECEPTOR ALPHA1; INTERLEUKIN 4; INTERLEUKIN 4 ANTIBODY; INTERLEUKIN 4 RECEPTOR; INTERLEUKIN 4 RECEPTOR ALPHA; INTERLEUKIN 4 RECEPTOR GAMMA C; INTERLEUKIN 4 RECEPTOR TYPE I; INTERLEUKIN 4 RECEPTOR TYPE II; JANUS KINASE; MDNA 55; MDNA 56; MDNA 57; MOLECULAR THERAPY AGENT; MONOCLONAL ANTIBODY; PASCOLIZUMAB; PHOSPHATIDYLINOSITOL 3 KINASE; PITRAKINRA; PROTEIN KINASE B; RUXOLITINIB; STAT6 PROTEIN; UNCLASSIFIED DRUG; JAK1 PROTEIN, HUMAN; JANUS KINASE 1;

ANTINEOPLASTIC ACTIVITY; DRUG TARGETING; EPITHELIUM TUMOR; GENE OVEREXPRESSION; HEMATOPOIETIC CELL; HUMAN; IMMUNOCOMPETENT CELL; METASTASIS; MOLECULARLY TARGETED THERAPY; NONHUMAN; PHARMACOLOGICAL BLOCKING; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN SUBUNIT; PROTEIN TARGETING; REVIEW; SIGNAL TRANSDUCTION; SOLID TUMOR; TUMOR MICROENVIRONMENT; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; NEOPLASMS, GLANDULAR AND EPITHELIAL; PATHOLOGY; PHYSIOLOGY;

HUMANS; INTERLEUKIN-4; JANUS KINASE 1; NEOPLASMS, GLANDULAR AND EPITHELIAL; RECEPTORS, INTERLEUKIN-4; SIGNAL TRANSDUCTION; STAT6 TRANSCRIPTION FACTOR; TUMOR MICROENVIRONMENT;

EID: 84947491595     PISSN: 02620898     EISSN: 15737276     Source Type: Journal    
DOI: 10.1007/s10585-015-9747-9     Document Type: Review

References (76)

1. Siegel RL, Miller KD, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65:5–29. doi:10.3322/caac.21254
2. Hallett MA, Venmar KT, Fingleton B (2012) Cytokine stimulation of epithelial cancer cells: the similar and divergent functions of IL-4 and IL-13. Cancer Res 72:6338–6343. doi:10.1158/0008-5472.CAN-12-3544
3. Li BH, Yang XZ, Li PD, Yuan Q, Liu XH, Yuan J, Zhang WJ (2008) IL-4/Stat6 activities correlate with apoptosis and metastasis in colon cancer cells. Biochem Biophys Res Commun 369:554–560. doi:10.1016/j.bbrc.2008.02.052
4. DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D, Kolhatkar N, Coussens LM (2009) CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell 16:91–102. doi:10.1016/j.ccr.2009.06.018
5. Venmar KT, Kimmel DW, Cliffel DE, Fingleton B (2015) IL4 receptor α mediates enhanced glucose and glutamine metabolism to support breast cancer growth. Biochim Biophys Acta 1853:1219–1228. doi:10.1016/j.bbamcr.2015.02.020
6. Venmar KT, Carter KJ, Hwang DG, Dozier EA, Fingleton B (2014) IL-4 receptor ILR4α regulates metastatic colonization by mammary tumors through multiple signaling pathways. Cancer Res. doi:10.1158/0008-5472.CAN-14-0093
7. Dufort FJ, Bleiman BF, Gumina MR, Blair D, Wagner DJ, Roberts MF, Abu-Amer Y, Chiles TC (2007) Cutting edge: IL-4-mediated protection of primary B lymphocytes from apoptosis via Stat6-dependent regulation of glycolytic metabolism. J Immunol 179:4953–4957
8. Wang R, Green DR (2012) Metabolic checkpoints in activated T cells. Nat Immunol 13:907–915. doi:10.1038/ni.2386
9. Martinez FO, Sica A, Mantovani A, Locati M (2008) Macrophage activation and polarization. Front Biosci 13:453–461
10. Nelms K, Keegan AD, Zamorano J, Ryan JJ, Paul WE (1999) The IL-4 receptor: signaling mechanisms and biologic functions. Annu Rev Immunol 17:701–738. doi:10.1146/annurev.immunol.17.1.701
11. Gallina G, Dolcetti L, Serafini P, De Santo C, Marigo I, Colombo MP, Basso G, Brombacher F, Borrello I, Zanovello P, Bicciato S, Bronte V (2006) Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. J Clin Invest 116:2777–2790. doi:10.1172/JCI28828
12. Surana R, Wang S, Xu W, Jablonski SA, Weiner LM (2014) IL4 limits the efficacy of tumor-targeted antibody therapy in a murine model. Cancer Immunol Res 2:1103–1112. doi:10.1158/2326-6066.CIR-14-0103
13. Todaro M, Lombardo Y, Francipane MG, Alea MP, Cammareri P, Iovino F, Di Stefano AB, Di Bernardo C, Agrusa A, Condorelli G, Walczak H, Stassi G (2008) Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4. Cell Death Differ 15:762–772. doi:10.1038/sj.cdd.4402305
14. Mueller TD, Zhang J-L, Sebald W, Duschl A (2002) Structure, binding, and antagonists in the IL-4/IL-13 receptor system. Biochim Biophys Acta 1592:237–250
15. Kotsimbos TC, Ghaffar O, Minshall EM, Humbert M, Durham SR, Pfister R, Menz G, Kay AB, Hamid QA (1998) Expression of the IL-4 receptor alpha-subunit is increased in bronchial biopsy specimens from atopic and nonatopic asthmatic subjects. J Allergy Clin Immunol 102:859–866
16. Andrews R, Rosa L, Daines M, Khurana Hershey G (2001) Reconstitution of a functional human type II IL-4/IL-13 receptor in mouse B cells: demonstration of species specificity. J Immunol 166:1716–1722
17. Dubois GR, Schweizer RC, Versluis C, Bruijnzeel-Koomen CA, Bruijnzeel PL (1998) Human eosinophils constitutively express a functional interleukin-4 receptor: interleukin-4—induced priming of chemotactic responses and induction of PI-3 kinase activity. Am J Respir Cell Mol Biol 19:691–699. doi:10.1165/ajrcmb.19.4.3208
18. Doucet C, Brouty-Boyé D, Pottin-Clémenceau C, Canonica GW, Jasmin C, Azzarone B (1998) Interleukin (IL) 4 and IL-13 act on human lung fibroblasts. Implication in asthma. J Clin Invest 101:2129–2139. doi:10.1172/JCI741
19. Van der Velden VH, Naber BA, Wierenga-Wolf AF, Debets R, Savelkoul HF, Overbeek SE, Hoogsteden HC, Versnel MA (1998) Interleukin 4 receptors on human bronchial epithelial cells. An in vivo and in vitro analysis of expression and function. Cytokine 10:803–813. doi:10.1006/cyto.1998.0365
20. Siddiqui S, Mistry V, Doe C, Stinson S, Foster M, Brightling C (2010) Airway wall expression of OX40/OX40L and interleukin-4 in asthma. Chest 137:797–804. doi:10.1378/chest.09-1839
21. Ito T, Suzuki S, Kanaji S, Shiraishi H, Ohta S, Arima K, Tanaka G, Tamada T, Honjo E, Garcia KC, Kuroki R, Izuhara K (2009) Distinct structural requirements for interleukin-4 (IL-4) and IL-13 binding to the shared IL-13 receptor facilitate cellular tuning of cytokine responsiveness. J Biol Chem 284:24289–24296. doi:10.1074/jbc.M109.007286
22. LaPorte SL, Juo ZS, Vaclavikova J, Colf LA, Qi X, Heller NM, Keegan AD, Garcia KC (2008) Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system. Cell 132:259–272. doi:10.1016/j.cell.2007.12.030
23. Obiri NI, Hillman GG, Haas GP, Sud S, Puri RK (1993) Expression of high affinity interleukin-4 receptors on human renal cell carcinoma cells and inhibition of tumor cell growth in vitro by interleukin-4. J Clin Invest 91:88–93. doi:10.1172/JCI116205
24. Obiri NI, Siegel JP, Varricchio F, Puri RK (1994) Expression of high-affinity IL-4 receptors on human melanoma, ovarian and breast carcinoma cells. Clin Exp Immunol 95:148–155
25. Leland P, Taguchi J, Husain SR, Kreitman RJ, Pastan I, Puri RK (2000) Human breast carcinoma cells express type II IL-4 receptors and are sensitive to antitumor activity of a chimeric IL-4-Pseudomonas exotoxin fusion protein in vitro and in vivo. Mol Med 6:165–178
26. Kioi M, Takahashi S, Kawakami M, Kawakami K, Kreitman RJ, Puri RK (2005) Expression and targeting of interleukin-4 receptor for primary and advanced ovarian cancer therapy. Cancer Res 65:8388–8396. doi:10.1158/0008-5472.CAN-05-1043
27. Puri RK, Leland P, Kreitman RJ, Pastan I (1994) Human neurological cancer cells express interleukin-4 (IL-4) receptors which are targets for the toxic effects of IL4-Pseudomonas exotoxin chimeric protein. Int J Cancer 58:574–581
28. Husain SR, Gill P, Kreitman RJ, Pastan I, Puri RK (1997) Interleukin-4 receptor expression on AIDS-associated Kaposi’s sarcoma cells and their targeting by a chimeric protein comprised of circularly permuted interleukin-4 and Pseudomonas exotoxin. Mol Med 3:327–338
29. Kawakami K, Leland P, Puri RK (2000) Structure, function, and targeting of interleukin 4 receptors on human head and neck cancer cells. Cancer Res 60:2981–2987
30. Clinicaltrials.gov (2015) https://clinicaltrials.gov. Accessed June 5, 2015
31. Kasaian MT, Miller DK (2008) IL-13 as a therapeutic target for respiratory disease. Biochem Pharmacol 76:147–155. doi:10.1016/j.bcp.2008.04.002
32. Conticello C, Pedini F, Zeuner A, Patti M, Zerilli M, Stassi G, Messina A, Peschle C, De Maria R (2004) IL-4 protects tumor cells from anti-CD95 and chemotherapeutic agents via up-regulation of antiapoptotic proteins. J Immunol 172:5467–5477
33. Roca H, Craig MJ, Ying C, Varsos ZS, Czarnieski P, Alva AS, Hernandez J, Fuller D, Daignault S, Healy PN, Pienta KJ (2011) IL-4 induces proliferation in prostate cancer PC3 cells under nutrient-depletion stress through the activation of the JNK-pathway and survivin upregulation. J Cell Biochem 113:1569–1580. doi:10.1002/jcb.24025
34. Prokopchuk O, Liu Y, Henne-Bruns D, Kornmann M (2005) Interleukin-4 enhances proliferation of human pancreatic cancer cells: evidence for autocrine and paracrine actions. Br J Cancer 92:921–928. doi:10.1038/sj.bjc.6602416
35. Maes T, Joos GF, Brusselle GG (2012) Targeting interleukin-4 in asthma: lost in translation? Am J Respir Cell Mol Biol 47:261–270. doi:10.1165/rcmb.2012-0080TR
36. Kuperman DA, Schleimer RP (2008) Interleukin-4, interleukin-13, signal transducer and activator of transcription factor 6, and allergic asthma. Curr Mol Med 8:384–392
37. Oh CK, Geba GP, Molfino N (2010) Investigational therapeutics targeting the IL-4/IL-13/STAT-6 pathway for the treatment of asthma. Eur Respir Rev 19:46–54. doi:10.1183/09059180.00007609
38. Murata T, Noguchi PD, Puri RK (1995) Receptors for interleukin (IL)-4 do not associate with the common chain, and IL-4 induces the phosphorylation of JAK2 tyrosine kinase in human colon carcinoma cells. J Biol Chem 270:30829–30836. doi:10.1074/jbc.270.51.30829
39. Delgoffe GM, Kole TP, Zheng Y, Zarek PE, Matthews KL, Xiao B, Worley PF, Kozma SC, Powell JD (2009) The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment. Immunity 30:832–844. doi:10.1016/j.immuni.2009.04.014
40. Miklossy G, Hilliard TS, Turkson J (2013) Therapeutic modulators of STAT signalling for human diseases. Nat Rev Drug Discov 12:611–629. doi:10.1038/nrd4088
41. Aaronson DS, Horvath CM (2002) A road map for those who don’t know JAK-STAT. Science 296:1653–1655. doi:10.1126/science.1071545
42. Li BH, Yang XZ, Li PD, Yuan Q, Liu XH, Yuan J, Zhang WJ (2008) IL-4/Stat6 activities correlate with apoptosis and metastasis in colon cancer cells. Biochem Biophys Res Commun 369:554–560. doi:10.1016/j.bbrc.2008.02.052
43. Siemasko KF, Chong AS, Williams JW, Bremer EG, Finnegan A (1996) Regulation of B cell function by the immunosuppressive agent leflunomide. Transplantation 61:635–642
44. Cherwinski HM, Byars N, Ballaron SJ, Nakano GM, Young JM, Ransom JT (1995) Leflunomide interferes with pyrimidine nucleotide biosynthesis. Inflamm Res 44:317–322
45. Mattar T, Kochhar K, Bartlett R, Bremer EG, Finnegan A (1993) Inhibition of the epidermal growth factor receptor tyrosine kinase activity by leflunomide. FEBS Lett 334:161–164
46. Friedman Ohana R, Kirkland TA, Woodroofe CC, Levin S, Uyeda HT, Otto P, Hurst R, Robers MB, Zimmerman K, Encell LP, Wood KV (2015) Deciphering the cellular targets of bioactive compounds using a chloroalkane capture tag. ACS Chem Biol. doi:10.1021/acschembio.5b00351
47. Gibeon D, Menzies-Gow AN (2012) Targeting interleukins to treat severe asthma. Expert Rev Respir Med 6:423–439. doi:10.1586/ers.12.38
48. Ohara J, Paul WE (1985) Production of a monoclonal antibody to and molecular characterization of B-cell stimulatory factor-1. Nature 315:333–336
49. Umansky V, Sevko A (2013) Tumor microenvironment and myeloid-derived suppressor cells. Cancer Microenviron 6:169–177. doi:10.1007/s12307-012-0126-7
50. Leen AM, Sukumaran S, Watanabe N, Mohammed S, Keirnan J, Yanagisawa R, Anurathapan U, Rendon D, Heslop HE, Rooney CM, Brenner MK, Vera JF (2014) Reversal of tumor immune inhibition using a chimeric cytokine receptor. Mol Ther 22:1211–1220. doi:10.1038/mt.2014.47
51. Wang H-W, Joyce JA (2010) Alternative activation of tumor-associated macrophages by IL-4: priming for protumoral functions. Cell Cycle 9:4824–4835
52. Qian B-Z, Pollard JW (2010) Macrophage diversity enhances tumor progression and metastasis. Cell 141:39–51. doi:10.1016/j.cell.2010.03.014
53. Roth F, De La Fuente AC, Vella JL, Zoso A, Inverardi L, Serafini P (2012) Aptamer-mediated blockade of IL4Rα triggers apoptosis of MDSCs and limits tumor progression. Cancer Res 72:1373–1383. doi:10.1158/0008-5472.CAN-11-2772
54. Beck LA, Thaçi D, Hamilton JD, Graham NM, Bieber T, Rocklin R, Ming JE, Ren H, Kao R, Simpson E, Ardeleanu M, Weinstein SP, Pirozzi G, Guttman-Yassky E, Suárez-Fariñas M, Hager MD, Stahl N, Yancopoulos GD, Radin AR (2014) Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med 371:130–139. doi:10.1056/NEJMoa1314768
55. Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, Wang L, Kirkesseli S, Rocklin R, Bock B, Hamilton J, Ming JE, Radin A, Stahl N, Yancopoulos GD, Graham N, Pirozzi G (2013) Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med 368:2455–2466. doi:10.1056/NEJMoa1304048
56. Duppatla V, Gjorgjevikj M, Schmitz W, Hermanns HM, Schäfer CM, Kottmair M, Müller T, Sebald W (2014) IL-4 analogues with site-specific chemical modification at position 121 inhibit IL-4 and IL-13 biological activities. Bioconjugate Chem 25:52–62. doi:10.1021/bc400307k
57. Todaro M, Alea MP, Di Stefano AB, Cammareri P, Vermeulen L, Iovino F, Tripodo C, Russo A, Gulotta G, Medema JP, Stassi G (2007) Colon cancer stem cells dictate tumor growth and resist cell death by production of interleukin-4. Cell Stem Cell 1:389–402. doi:10.1016/j.stem.2007.08.001
58. Gandhi H, Worch R, Kurgonaite K, Hintersteiner M, Schwille P, Bökel C, Weidemann T (2014) Dynamics and interaction of interleukin-4 receptor subunits in living cells. Biophys J 107:2515–2527. doi:10.1016/j.bpj.2014.07.077
59. Kruse N, Tony HP, Sebald W (1992) Conversion of human interleukin-4 into a high affinity antagonist by a single amino acid replacement. EMBO J 11:3237–3244
60. Kruse N, Tony HP, Sebald W (1992) Conversion of human interleukin-4 into a high affinity antagonist by a single amino acid replacement. EMBO J 11:3237–3244
61. Zhang J-L, Buehner M, Sebald W (2002) Functional epitope of common gamma chain for interleukin-4 binding. Eur J Biochem 269:1490–1499
62. Junttila IS, Creusot RJ, Moraga I, Bates DL, Wong MT, Alonso MN, Suhoski MM, Lupardus P, Meier-Schellersheim M, Engleman EG, Utz PJ, Fathman CG, Paul WE, Garcia KC (2012) Redirecting cell-type specific cytokine responses with engineered interleukin-4 superkines. Nat Chem Biol 8:990–998. doi:10.1038/nchembio.1096
63. Medicenna Therapeutics Inc. https://medicenna.com. Accessed June 5, 2015
64. Kienzle N, Olver S, Buttigieg K, Groves P, Janas ML, Baz A, Kelso A (2005) Progressive differentiation and commitment of CD8+ T cells to a poorly cytolytic CD8 low phenotype in the presence of IL-4. J Immunol 174:2021–2029
65. Kienzle N, Buttigieg K, Groves P, Kawula T, Kelso A (2002) A clonal culture system demonstrates that IL-4 induces a subpopulation of noncytolytic T cells with low CD8, perforin, and granzyme expression. J Immunol 168:1672–1681
66. Helmich BK, Dutton RW (2001) The role of adoptively transferred CD8 T cells and host cells in the control of the growth of the EG7 thymoma: factors that determine the relative effectiveness and homing properties of Tc1 and Tc2 effectors. J Immunol 166:6500–6508
67. Kemp RA, Ronchese F (2001) Tumor-specific Tc1, but not Tc2, cells deliver protective antitumor immunity. J Immunol 167:6497–6502
68. Yang L, DeBusk LM, Fukuda K, Fingleton B, Green-Jarvis B, Shyr Y, Matrisian LM, Carbone DP, Lin PC (2004) Expansion of myeloid immune suppressor Gr + CD11b + cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6:409–421. doi:10.1016/j.ccr.2004.08.031
69. Van Kempen LCL, Coussens LM (2002) MMP9 potentiates pulmonary metastasis formation. Cancer Cell 2:251–252
70. Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9:162–174. doi:10.1038/nri2506
71. Pollard JW (2004) Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer 4:71–78. doi:10.1038/nrc1256
72. Srabovici N, Mujagic Z, Mujanovic-Mustedanagic J, Muminovic Z, Softic A, Begic L (2011) Interleukin 13 expression in the primary breast cancer tumour tissue. Biochem medica 21:131–138
73. Gabitass RF, Annels NE, Stocken DD, Pandha HA, Middleton GW (2011) Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13. Cancer Immunol Immunother 60:1419–1430. doi:10.1007/s00262-011-1028-0
74. Ostojic A, Vrhovac R, Verstovsek S (2011) Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. Future Oncol 7:1035–1043. doi:10.2217/fon.11.81
75. Borish LC, Nelson HS, Lanz MJ, Claussen L, Whitmore JB, Agosti JM, Garrison L (1999) Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial. Am J Respir Crit Care Med 160:1816–1823. doi:10.1164/ajrccm.160.6.9808146
76. Hart TK, Blackburn MN, Brigham-Burke M, Dede K, Al-Mahdi N, Zia-Amirhosseini P, Cook RM (2002) Preclinical efficacy and safety of pascolizumab (SB 240683): a humanized anti-interleukin-4 antibody with therapeutic potential in asthma. Clin Exp Immunol 130:93–100