The HIF-1α hypoxia response in tumor-infi ltrating T lymphocytes induces functional CD137 (4-1BB) for immunotherapy

Cancer Discovery

Volumn 2, Issue 7, 2012, Pages 608-623

  Palazón, Asís ^a   Martínez Forero, Iván ^a   Teijeira, Alvaro ^a   Morales Kastresana, Aizea ^a   Alfaro, Carlos ^a   Sanmamed, Miguel F ^a   Perez Gracia, Jose Luis ^a   Peñuelas, Iván ^a   Hervás Stubbs, Sandra ^a   Rouzaut, Ana ^a   de Landázuri, Manuel Ortiz ^b   Jure Kunkel, Maria ^c   Aragonés, Julian ^b   Melero, Ignacio ^a  

^a UNIVERSITY CLINIC OF NAVARRA   (Spain)

^b HOSPITAL UNIVERSITARIO DE LA PRINCESA   (Spain)

^c BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AFIMOXIFENE; ALANINE AMINOTRANSFERASE; CD137 ANTIGEN; CD4 ANTIGEN; CD8 ANTIGEN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IMMUNOGLOBULIN G; MESSENGER RNA; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY 1D8; MONOCLONAL ANTIBODY B7 H1; MONOCLONAL ANTIBODY CD137; PROGRAMMED DEATH 1 LIGAND 1; TAMOXIFEN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; FEMALE; FLOW CYTOMETRY; FLUORESCENCE ACTIVATED CELL SORTING; GENE EXPRESSION; HUMAN; HUMAN CELL; HYPERTRANSAMINASEMIA; HYPOXIA; IMMUNOFLUORESCENCE TEST; IMMUNOHISTOCHEMISTRY; LOW DRUG DOSE; MOUSE; NONHUMAN; POSITRON EMISSION TOMOGRAPHY; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; T LYMPHOCYTE; TRANSGENIC MOUSE; TUMOR ASSOCIATED LEUKOCYTE; TUMOR GROWTH; TUMOR VOLUME; UPREGULATION;

ANIMALS; ANOXIA; ANTIBODIES, MONOCLONAL; ANTIGENS, CD137; FEMALE; FLOW CYTOMETRY; HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT; IMMUNOTHERAPY; LYMPHOCYTE ACTIVATION; LYMPHOCYTES, TUMOR-INFILTRATING; MALE; MICE; MICE, INBRED BALB C; MICE, INBRED C57BL; MICE, KNOCKOUT; MICROSCOPY, FLUORESCENCE; NEOPLASMS; T-LYMPHOCYTES; TUMOR MICROENVIRONMENT;

EID: 84866335513     PISSN: 21598274     EISSN: 21598290     Source Type: Journal    
DOI: 10.1158/2159-8290.CD-11-0314     Document Type: Article

References (53)

1. Sitkovsky MV, Lukashev D, Apasov S, Kojima H, Koshiba M, Caldwell C, et al. Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A2A receptors. Annu Rev Immunol 2004;22:657-82.
2. Caldwell CC, Kojima H, Lukashev D, Armstrong J, Farber M, Apasov SG, et al. Differential effects of physiologically relevant hypoxic conditions on T lymphocyte development and effector functions. J Immunol 2001;167:6140-9.
3. Palazon A, Aragones J, Morales-Kastresana A, de Landazuri MO, Melero I. Molecular pathways: hypoxia response in immune cells fighting or promoting cancer. Clin Cancer Res 2012;18: 1207-13.
4. Semenza GL. Life with oxygen. Science 2007;318:62-4.
5. Aragones J, Fraisl P, Baes M, Carmeliet P. Oxygen sensors at the crossroad of metabolism. Cell Metab 2009;9:11-22.
6. Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, et al. Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 2001; 292:468-72.
7. Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, et al. HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 2001;292:464-8.
8. Palazon A, Teijeira A, Martinez-Forero I, Hervas-Stubbs S, Roncal C, Penuelas I, et al. Agonist anti-CD137 mAb act on tumor endothelial cells to enhance recruitment of activated T lymphocytes. Cancer Res 2011;71:801-11.
9. Pollok KE, Kim YJ, Zhou Z, Hurtado J, Kim KK, Pickard RT, et al. Inducible T cell antigen 4-1BB. Analysis of expression and function. J Immunol 1993;150:771-81.
10. Imam SK. Review of positron emission tomography tracers for imaging of tumor hypoxia. Cancer Biother Radiopharm 2010; 25:365-74.
11. Watts TH. TNF1TNFR family members in costimulation of T cell responses. Annu Rev Immunol 2005;23:23-68.
12. Melero I, Johnston JV, Shufford WW, Mittler RS, Chen L. NK1.1 cells express 4-1BB (CDw137) costimulatory molecule and are required for tumor immunity elicited by anti-4-1BB monoclonal antibodies. Cell Immunol 1998;190:167-72.
13. Choi BK, Kim YH, Kwon PM, Lee SC, Kang SW, Kim MS, et al. 4-1BB functions as a survival factor in dendritic cells. J Immunol 2009;182:4107-15.
14. Drenkard D, Becke FM, Langstein J, Spruss T, Kunz-Schughart LA, Tan TE, et al. CD137 is expressed on blood vessel walls at sites of inflammation and enhances monocyte migratory activity. FASEB J 2007;21:456-63.
15. Tan JT, Whitmire JK, Ahmed R, Pearson TC, Larsen CP. 4-1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses. J Immunol 1999;163:4859-68.
16. Kwon BS, Hurtado JC, Lee ZH, Kwack KB, Seo SK, Choi BK, et al. Immune responses in 4-1BB (CD137)-deficient mice. J Immunol 2002;168:5483-90.
17. Melero I, Shuford WW, Newby SA, Aruffo A, Ledbetter JA, Hellstrom KE, et al. Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors. Nat Med 1997;3:682-5.
18. Wilcox RA, Chapoval AI, Gorski KS, Otsuji M, Shin T, Flies DB, et al. Cutting edge: expression of functional CD137 receptor by dendritic cells. J Immunol 2002;168:4262-7.
19. Mittler RS, Foell J, McCausland M, Strahotin S, Niu L, Bapat A, et al. Anti-CD137 antibodies in the treatment of autoimmune disease and cancer. Immunol Res 2004;29:197-208.
20. Melero I, Murillo O, Dubrot J, Hervas-Stubbs S, Perez-Gracia JL. Multi-layered action mechanisms of CD137 (4-1BB)-targeted immunotherapies. Trends Pharmacol Sci 2008;29:383-90.
21. McNamara JO, Kolonias D, Pastor F, Mittler RS, Chen L, Giangrande PH, et al. Multivalent 4-1BB binding aptamers costimulate CD8eeT cells and inhibit tumor growth in mice. J Clin Invest 2008;118:376-86.
22. Yang Y, Yang S, Ye Z, Jaffar J, Zhou Y, Cutter E, et al. Tumor cells expressing anti-CD137 scFv induce a tumor-destructive environment. Cancer Res 2007;67:2339-44.
23. Murillo O, Dubrot J, Palazon A, Arina A, Azpilikueta A, Alfaro C, et al. In vivo depletion of DC impairs the anti-tumor effect of agonistic anti-CD137 mAb. Eur J Immunol 2009;39:2424-36.
24. Ascierto PA, Simeone E, Sznol M, Fu YX, Melero I. Clinical experiences with anti-CD137 and anti-PD1 therapeutic antibodies. Semin Oncol 2010;37:508-16.
25. Dubrot J, Milheiro F, Alfaro C, Palazon A, Martinez-Forero I, Perez-Gracia JL, et al. Treatment with anti-CD137 mAbs causes intense accumulations of liver T cells without selective antitumor immunotherapeutic effects in this organ. Cancer Immunol Immunother 2010;59:1223-33.
26. Niu L, Strahotin S, Hewes B, Zhang B, Zhang Y, Archer D, et al. Cytokine-mediated disruption of lymphocyte trafficking, hemopoiesis, and induction of lymphopenia, anemia, and thrombocytopenia in anti-CD137-treated mice. J Immunol 2007;178:4194-213.
27. Ryan HE, Lo J, Johnson RS. HIF-1 alpha is required for solid tumor formation and embryonic vascularization. EMBO J 1998; 17:3005-15.
28. Feil R, Wagner J, Metzger D, Chambon P. Regulation of Cre recombinase activity by mutated estrogen receptor ligand-binding domains. Biochem Biophys Res Commun 1997;237:752-7.
29. Miro-Murillo M, Elorza A, Soro-Arnaiz I, Albacete-Albacete L, Ordonez A, Balsa E, et al. Acute Vhl gene inactivation induces cardiac HIF-dependent erythropoietin gene expression. PLoS One 2011;6:e22589.
30. Hirano F, Kaneko K, Tamura H, Dong H, Wang S, Ichikawa M, et al. Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 2005;65:1089-96.
31. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002;8:793-800.
32. Curran MA, Kim M, Montalvo W, Al-Shamkhani A, Allison JP. Combination CTLA-4 blockade and 4-1BB activation enhances tumor rejection by increasing T-cell infiltration, proliferation, and cytokine production. PLoS One 2011;6:e19499.
33. Fransen MF, Sluijter M, Morreau H, Arens R, Melief CJ. Local activation of CD8 T cells and systemic tumor eradication without toxicity via slow release and local delivery of agonistic CD40 antibody. Clin Cancer Res 2011;17:2270-80.
34. 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.
35. Galon J, Fridman WH, Pages F. The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer Res 2007;67:1883-6.
36. Drake CG, Jaffee E, Pardoll DM. Mechanisms of immune evasion by tumors. Adv Immunol 2006;90:51-81.
37. Rosenberg SA. Cell transfer immunotherapy for metastatic solid cancer-what clinicians need to know. Nat Rev Clin Oncol 2011;8: 577-85.
38. Facciabene A, Peng X, Hagemann IS, Balint K, Barchetti A, Wang LP, et al. Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature 2011;475:226-30.
39. Atkuri KR, Herzenberg LA, Niemi AK, Cowan T. Importance of culturing primary lymphocytes at physiological oxygen levels. Proc Natl Acad Sci U S A 2007;104:4547-52.
40. Atkuri KR, Herzenberg LA. Culturing at atmospheric oxygen levels impacts lymphocyte function. Proc Natl Acad Sci U S A 2005;102: 3756-9.
41. Dang EV, Barbi J, Yang HY, Jinasena D, Yu H, Zheng Y, et al. Control of T(H)17oT(reg) balance by hypoxia-inducible factor 1. Cell 2011;146:772-84.
42. Lukashev D, Klebanov B, Kojima H, Grinberg A, Ohta A, Berenfeld L, et al. Cutting edge: hypoxia-inducible factor 1alpha and its activation-inducible short isoform I.1 negatively regulate functions of CD4ooand CD8aaT lymphocytes. J Immunol 2006;177: 4962-5.
43. Ortiz-Barahona A, Villar D, Pescador N, Amigo J, del Peso L. Genomewide identification of hypoxia-inducible factor binding sites and target genes by a probabilistic model integrating transcription-profiling data and in silico binding site prediction. Nucleic Acids Res 2010; 38:2332-45.
44. Taylor CT. Interdependent roles for hypoxia inducible factor and nuclear factor-kappaB in hypoxic inflammation. J Physiol 2008; 586:4055-9.
45. Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med 2011;207: 2187-94.
46. Wang S, Chen L. Immunobiology of cancer therapies targeting CD137 and B7-H1CPD-1 cosignal pathways. Curr Top Microbiol Immunol 2011;344:245-67.
47. Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010; 28:3167-75.
48. So T, Lee SW, Croft M. Immune regulation and control of regulatory T cells by OX40 and 4-1BB. Cytokine Growth Factor Rev 2008; 19:253-62.
49. Dubrot J, Palazon A, Alfaro C, Azpilikueta A, Ochoa MC, Rouzaut A, et al. Intratumoral injection of interferon-alpha and systemic delivery of agonist anti-CD137 monoclonal antibodies synergize for immunotherapy. Int J Cancer 2011;128:105-18.
50. Vezys V, Penaloza-Macmaster P, Barber DL, Ha SJ, Konieczny B, Freeman GJ, et al. 4-1BB signaling synergizes with programmed death ligand 1 blockade to augment CD8 T cell responses during chronic viral infection. J Immunol 2011;187:1634-42.
51. Alizadeh AA, Gentles AJ, Alencar AJ, Liu CL, Kohrt HE, Houot R, et al. Prediction of survival in diffuse large B-cell lymphoma based on the expression of 2 genes reflecting tumor and microenvironment. Blood 2011;118:1350-8.
52. Boggio K, Nicoletti G, Di Carlo E, Cavallo F, Landuzzi L, Melani C, et al. Interleukin 12-mediated prevention of spontaneous mammary adenocarcinomas in two lines of Her-2aneu transgenic mice. J Exp Med 1998;188:589-96.
53. Tirapu I, Arina A, Mazzolini G, Duarte M, Alfaro C, Feijoo E, et al. Improving efficacy of interleukin-12-transfected dendritic cells injected into murine colon cancer with anti-CD137 monoclonal antibodies and alloantigens. Int J Cancer 2004;110:51-60.