Top

Published in:

01-03-2011

Angiogenesis and immunity: a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy

Authors: Eric Tartour, H. Pere, B. Maillere, M. Terme, N. Merillon, J. Taieb, F. Sandoval, F. Quintin-Colonna, K. Lacerda, A. Karadimou, C. Badoual, A. Tedgui, W. H. Fridman, S. Oudard

Published in: Cancer and Metastasis Reviews | Issue 1/2011

Abstract

The immune system regulates angiogenesis in cancer with both pro- and antiangiogenic activities. The induction of angiogenesis is mediated by tumor-associated macrophages and myeloid-derived suppressor cells (MDSC) which produce proinflammatory cytokines, endothelial growth factors (VEGF, bFGF…), and protease (MMP9) implicated in neoangiogenesis. Some cytokines (IL-6, IL-17…) activated Stat3 which also led to the production of VEGF and bFGF. In contrast, other cytokines (IFN, IL-12, IL-21, and IL-27) display an antiangiogenic activity. Recently, it has been shown that some antiangiogenic molecules alleviates immunosuppression associated with cancer by decreasing immunosuppressive cells (MDSC, regulatory T cells), immunosuppressive cytokines (IL-10, TGFβ), and inhibitory molecules on T cells (PD-1). Some of these broad effects may result from the ability of some antiangiogenic molecules, especially cytokines to inhibit the Stat3 transcription factor. The association often observed between angiogenesis and immunosuppression may be related to hypoxia which induces both neoangiogenesis via activation of HIF-1 and VEGF and favors the intratumor recruitment and differentiation of regulatory T cells and MDSC. Preliminary studies suggest that modulation of immune markers (intratumoral MDSC and IL-8, peripheral regulatory T cells…) may predict clinical response to antiangiogenic therapy. In preclinical models, a synergy has been observed between antiangiogenic molecules and immunotherapy which may be explained by an improvement of immune status in tumor-bearing mice after antiangiogenic therapy. In preclinical models, antiangiogenic molecules promoted intratumor trafficking of effector cells, enhance endogenous anti-tumor response, and synergyzed with immunotherapy protocols to cure established murine tumors. All these results warrant the development of clinical trials combining antiangiogenic drugs and immunotherapy.

Oudard, S., George, D., Medioni, J., & Motzer, R. (2007). Treatment options in renal cell carcinoma: Past, present and future. Annals of Oncology, 18(Suppl 10), x25–x31.PubMed

Rini, B. I., Campbell, S. C., & Escudier, B. (2009). Renal cell carcinoma. Lancet, 373, 1119–1132.PubMed

Oudard, S., Medioni, J., Aylllon, J., Barrascourt, E., Elaidi, R. T., Balcaceres, J., et al. (2009). Everolimus (RAD001): An mTOR inhibitor for the treatment of metastatic renal cell carcinoma. Expert Review of Anticancer Therapy, 9, 705–717.PubMed

Motzer, R. J., Hutson, T. E., Tomczak, P., Michaelson, M. D., Bukowski, R. M., Rixe, O., et al. (2007). Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. The New England Journal of Medicine, 356, 115–124.PubMed

Barrascout, E., Medioni, J., Scotte, F., Ayllon, J., Mejean, A., Cuenod, C. A., et al. (2010). Angiogenesis inhibition: Review of the activity of sorafenib, sunitinib and bevacizumab. Bulletin du Cancer, 97, 29–43.PubMed

Escudier, B., Bellmunt, J., Negrier, S., Bajetta, E., Melichar, B., Bracarda, S., et al. (2010). Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): Final analysis of overall survival. Journal of Clinical Oncology, 28, 2144–2150.PubMed

Rini, B. I., Halabi, S., Rosenberg, J. E., Stadler, W. M., Vaena, D. A., Archer, L., et al. (2010). Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: Final results of CALGB 90206. Journal of Clinical Oncology, 28, 2137–2143.PubMed

Motzer, R. J., Escudier, B., Oudard, S., Hutson, T. E., Porta, C., Bracarda, S., et al. (2008). Efficacy of everolimus in advanced renal cell carcinoma: A double-blind, randomised, placebo-controlled phase III trial. Lancet, 372, 449–456.PubMed

Van Meter, M. E., & Kim, E. S. (2010). Bevacizumab: Current updates in treatment. Current Opinion in Oncology, 22, 586–591.PubMed

10.

Paez-Ribes, M., Allen, E., Hudock, J., Takeda, T., Okuyama, H., Vinals, F., et al. (2009). Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell, 15, 220–231.PubMed

11.

Ebos, J. M., Lee, C. R., Cruz-Munoz, W., Bjarnason, G. A., Christensen, J. G., & Kerbel, R. S. (2009). Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell, 15, 232–239.PubMed

12.

Rini, B. I., & Flaherty, K. (2008). Clinical effect and future considerations for molecularly-targeted therapy in renal cell carcinoma. Urologic Oncology, 26, 543–549.PubMed

13.

Albini, A., Tosetti, F., Benelli, R., & Noonan, D. M. (2005). Tumor inflammatory angiogenesis and its chemoprevention. Cancer Research, 65, 10637–10641.PubMed

14.

de Visser, K. E., Eichten, A., & Coussens, L. M. (2006). Paradoxical roles of the immune system during cancer development. Nature Reviews. Cancer, 6, 24–37.PubMed

15.

Murdoch, C., Muthana, M., Coffelt, S. B., & Lewis, C. E. (2008). The role of myeloid cells in the promotion of tumour angiogenesis. Nature Reviews. Cancer, 8, 618–631.PubMed

16.

Sunderkotter, C., Steinbrink, K., Goebeler, M., Bhardwaj, R., & Sorg, C. (1994). Macrophages and angiogenesis. Journal of Leukocyte Biology, 55, 410–422.PubMed

17.

Kimura, Y. N., Watari, K., Fotovati, A., Hosoi, F., Yasumoto, K., Izumi, H., et al. (2007). Inflammatory stimuli from macrophages and cancer cells synergistically promote tumor growth and angiogenesis. Cancer Science, 98, 2009–2018.PubMed

18.

Lewis, C. E., Leek, R., Harris, A., & McGee, J. O. (1995). Cytokine regulation of angiogenesis in breast cancer: The role of tumor-associated macrophages. Journal of Leukocyte Biology, 57, 747–751.PubMed

19.

Mantovani, A., Schioppa, T., Porta, C., Allavena, P., & Sica, A. (2006). Role of tumor-associated macrophages in tumor progression and invasion. Cancer and Metastasis Reviews, 25, 315–322.PubMed

20.

Grunewald, M., Avraham, I., Dor, Y., Bachar-Lustig, E., Itin, A., Jung, S., et al. (2006). VEGF-induced adult neovascularization: Recruitment, retention, and role of accessory cells. Cell, 124, 175–189.PubMed

21.

Du, R., Lu, K. V., Petritsch, C., Liu, P., Ganss, R., Passegue, E., et al. (2008). HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell, 13, 206–220.PubMed

22.

Giraudo, E., Inoue, M., & Hanahan, D. (2004). An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. The Journal of Clinical Investigation, 114, 623–633.PubMed

23.

Neufeld, G., & Kessler, O. (2006). Pro-angiogenic cytokines and their role in tumor angiogenesis. Cancer and Metastasis Reviews, 25, 373–385.PubMed

24.

Kim, Y. M., Lee, Y. M., Kim, H. S., Kim, J. D., Choi, Y., Kim, K. W., et al. (2002). TNF-related activation-induced cytokine (TRANCE) induces angiogenesis through the activation of Src and phospholipase C (PLC) in human endothelial cells. The Journal of Biological Chemistry, 277, 6799–6805.PubMed

25.

Silva-Santos, B. (2010). Promoting angiogenesis within the tumor microenvironment: The secret life of murine lymphoid IL-17-producing gammadelta T cells. European Journal of Immunology, 40, 1873–1876.PubMed

26.

Numasaki, M., Fukushi, J., Ono, M., Narula, S. K., Zavodny, P. J., Kudo, T., et al. (2003). Interleukin-17 promotes angiogenesis and tumor growth. Blood, 101, 2620–2627.PubMed

27.

Zou, W., & Restifo, N. P. (2010). T(H)17 cells in tumour immunity and immunotherapy. Nature Reviews. Immunology, 10, 248–256.PubMed

28.

Numasaki, M., Watanabe, M., Suzuki, T., Takahashi, H., Nakamura, A., McAllister, F., et al. (2005). IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR-2-dependent angiogenesis. Journal of Immunology, 175, 6177–6189.

29.

Ciree, A., Michel, L., Camilleri-Broet, S., Jean Louis, F., Oster, M., Flageul, B., et al. (2004). Expression and activity of IL-17 in cutaneous T-cell lymphomas (mycosis fungoides and Sezary syndrome). International Journal of Cancer, 112, 113–120.

30.

Pickens, S. R., Volin, M. V., Mandelin, A. M., 2nd, Kolls, J. K., Pope, R. M., & Shahrara, S. (2010). IL-17 contributes to angiogenesis in rheumatoid arthritis. Journal of Immunology, 184, 3233–3241.

31.

Kuniyasu, H., Ohmori, H., Sasaki, T., Sasahira, T., Yoshida, K., Kitadai, Y., et al. (2003). Production of interleukin 15 by human colon cancer cells is associated with induction of mucosal hyperplasia, angiogenesis, and metastasis. Clinical Cancer Research, 9, 4802–4810.PubMed

32.

Badoual, C., Bouchaud, G., Agueznay Nel, H., Mortier, E., Hans, S., Gey, A., et al. (2008). The soluble alpha chain of interleukin-15 receptor: A proinflammatory molecule associated with tumor progression in head and neck cancer. Cancer Research, 68, 3907–3914.PubMed

33.

Yu, H., Kortylewski, M., & Pardoll, D. (2007). Crosstalk between cancer and immune cells: Role of STAT3 in the tumour microenvironment. Nature Reviews. Immunology, 7, 41–51.PubMed

34.

Badoual, C., Sandoval, F., Pere, H., Hans, S., Gey, A., Merillon, N., et al. (2010). Better understanding tumor-host interaction in head and neck cancer to improve the design and development of immunotherapeutic strategies. Head & Neck, 32, 946–958.

35.

Voest, E. E., Kenyon, B. M., O’Reilly, M. S., Truitt, G., D’Amato, R. J., & Folkman, J. (1995). Inhibition of angiogenesis in vivo by interleukin 12. Journal of the National Cancer Institute, 87, 581–586.PubMed

36.

Sgadari, C., Angiolillo, A. L., & Tosato, G. (1996). Inhibition of angiogenesis by interleukin-12 is mediated by the interferon-inducible protein 10. Blood, 87, 3877–3882.PubMed

37.

Haicheur, N., Escudier, B., Dorval, T., Negrier, S., De Mulder, P. H., Dupuy, J. M., et al. (2000). Cytokines and soluble cytokine receptor induction after IL-12 administration in cancer patients. Clinical and Experimental Immunology, 119, 28–37.PubMed

38.

Dias, S., Boyd, R., & Balkwill, F. (1998). IL-12 regulates VEGF and MMPs in a murine breast cancer model. International Journal of Cancer, 78, 361–365.

39.

Dinney, C. P., Bielenberg, D. R., Perrotte, P., Reich, R., Eve, B. Y., Bucana, C. D., et al. (1998). Inhibition of basic fibroblast growth factor expression, angiogenesis, and growth of human bladder carcinoma in mice by systemic interferon-alpha administration. Cancer Research, 58, 808–814.PubMed

40.

Mitola, S., Strasly, M., Prato, M., Ghia, P., & Bussolino, F. (2003). IL-12 regulates an endothelial cell-lymphocyte network: Effect on metalloproteinase-9 production. Journal of Immunology, 171, 3725–3733.

41.

Shimizu, M., Shimamura, M., Owaki, T., Asakawa, M., Fujita, K., Kudo, M., et al. (2006). Antiangiogenic and antitumor activities of IL-27. Journal of Immunology, 176, 7317–7324.

42.

Castermans, K., Tabruyn, S. P., Zeng, R., van Beijnum, J. R., Eppolito, C., Leonard, W. J., et al. (2008). Angiostatic activity of the antitumor cytokine interleukin-21. Blood, 112, 4940–4947.PubMed

43.

Tartour, E., Mathiot, C., & Fridman, W. H. (1992). Current status of interleukin-2 therapy in cancer. Biomedicine & Pharmacotherapy, 46, 473–484.

44.

Ellis, L. M., & Hicklin, D. J. (2008). VEGF-targeted therapy: Mechanisms of anti-tumour activity. Nature Reviews. Cancer, 8, 579–591.PubMed

45.

Belkaid, Y., & Oldenhove, G. (2008). Tuning microenvironments: Induction of regulatory T cells by dendritic cells. Immunity, 29, 362–371.PubMed

46.

Curiel, T. J. (2007). Tregs and rethinking cancer immunotherapy. The Journal of Clinical Investigation, 117, 1167–1174.PubMed

47.

Oyama, T., Ran, S., Ishida, T., Nadaf, S., Kerr, L., Carbone, D. P., et al. (1998). Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells. Journal of Immunology, 160, 1224–1232.

48.

Dikov, M. M., Ohm, J. E., Ray, N., Tchekneva, E. E., Burlison, J., Moghanaki, D., et al. (2005). Differential roles of vascular endothelial growth factor receptors 1 and 2 in dendritic cell differentiation. Journal of Immunology, 174, 215–222.

49.

Gabrilovich, D. I., Ishida, T., Nadaf, S., Ohm, J. E., & Carbone, D. P. (1999). Antibodies to vascular endothelial growth factor enhance the efficacy of cancer immunotherapy by improving endogenous dendritic cell function. Clinical Cancer Research, 5, 2963–2970.PubMed

50.

Batchelor, T. T., Sorensen, A. G., di Tomaso, E., Zhang, W. T., Duda, D. G., Cohen, K. S., et al. (2007). AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell, 11, 83–95.PubMed

51.

Laxmanan, S., Robertson, S. W., Wang, E., Lau, J. S., Briscoe, D. M., & Mukhopadhyay, D. (2005). Vascular endothelial growth factor impairs the functional ability of dendritic cells through Id pathways. Biochemical and Biophysical Research Communications, 334, 193–198.PubMed

52.

Ohm, J. E., Shurin, M. R., Esche, C., Lotze, M. T., Carbone, D. P., & Gabrilovich, D. I. (1999). Effect of vascular endothelial growth factor and FLT3 ligand on dendritic cell generation in vivo. Journal of Immunology, 163, 3260–3268.

53.

Gabrilovich, D. I., Chen, H. L., Girgis, K. R., Cunningham, H. T., Meny, G. M., Nadaf, S., et al. (1996). Production of vascular endothelial growth factor by human tumors inhibits the functional maturation of dendritic cells. Natural Medicines, 2, 1096–1103.

54.

Ishida, T., Oyama, T., Carbone, D. P., & Gabrilovich, D. I. (1998). Defective function of Langerhans cells in tumor-bearing animals is the result of defective maturation from hemopoietic progenitors. Journal of Immunology, 161, 4842–4851.

55.

Osada, T., Chong, G., Tansik, R., Hong, T., Spector, N., Kumar, R., et al. (2008). The effect of anti-VEGF therapy on immature myeloid cell and dendritic cells in cancer patients. Cancer Immunology, Immunotherapy, 57, 1115–1124.PubMed

56.

Fricke, I., Mirza, N., Dupont, J., Lockhart, C., Jackson, A., Lee, J. H., et al. (2007). Vascular endothelial growth factor-trap overcomes defects in dendritic cell differentiation but does not improve antigen-specific immune responses. Clinical Cancer Research, 13, 4840–4848.PubMed

57.

Strauss, L., Volland, D., Kunkel, M., & Reichert, T. E. (2005). Dual role of VEGF family members in the pathogenesis of head and neck cancer (HNSCC): Possible link between angiogenesis and immune tolerance. Medical Science Monitor, 11, BR280–292.PubMed

58.

Almand, B., Resser, J. R., Lindman, B., Nadaf, S., Clark, J. I., Kwon, E. D., et al. (2000). Clinical significance of defective dendritic cell differentiation in cancer. Clinical Cancer Research, 6, 1755–1766.PubMed

59.

Boissel, N., Rousselot, P., Raffoux, E., Cayuela, J. M., Maarek, O., Charron, D., et al. (2004). Defective blood dendritic cells in chronic myeloid leukemia correlate with high plasmatic VEGF and are not normalized by imatinib mesylate. Leukemia, 18, 1656–1661.PubMed

60.

Finke, J. H., Rini, B., Ireland, J., Rayman, P., Richmond, A., Golshayan, A., et al. (2008). Sunitinib reverses type-1 immune suppression and decreases T-regulatory cells in renal cell carcinoma patients. Clinical Cancer Research, 14, 6674–6682.PubMed

61.

Hipp, M. M., Hilf, N., Walter, S., Werth, D., Brauer, K. M., Radsak, M. P., et al. (2008). Sorafenib, but not sunitinib, affects function of dendritic cells and induction of primary immune responses. Blood, 111, 5610–5620.PubMed

62.

Adotevi, O., Pere, H., Ravel, P., Haicheur, N., Badoual, C., Merillon, N., et al. (2010). A decrease of regulatory T cells correlates with overall survival after sunitinib-based antiangiogenic therapy in metastatic renal cancer patients. J Immunother, 33, 991–998.

63.

Abe, F., Younos, I., Westphal, S., Samson, H., Scholar, E., Dafferner, A., et al. (2010). Therapeutic activity of sunitinib for Her2/neu induced mammary cancer in FVB mice. International Immunopharmacology, 10, 140–145.PubMed

64.

Badoual, C., Hans, S., Rodriguez, J., Peyrard, S., Klein, C., Agueznay Nel, H., et al. (2006). Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clinical Cancer Research, 12, 465–472.PubMed

65.

Badoual, C., Hans, S., Fridman, W. H., Brasnu, D., Erdman, S., & Tartour, E. (2009). Revisiting the prognostic value of regulatory T cells in patients with cancer. Journal of Clinical Oncology, 27, e5–6. author reply e7.PubMed

66.

Suzuki, H., Onishi, H., Wada, J., Yamasaki, A., Tanaka, H., Nakano, K., et al. (2010). VEGFR2 is selectively expressed by FOXP3high CD4+ Treg. European Journal of Immunology, 40, 197–203.PubMed

67.

Ko, J. S., Zea, A. H., Rini, B. I., Ireland, J. L., Elson, P., Cohen, P., et al. (2009). Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clinical Cancer Research, 15, 2148–2157.PubMed

68.

Huang, B., Pan, P. Y., Li, Q., Sato, A. I., Levy, D. E., Bromberg, J., et al. (2006). Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host. Cancer Research, 66, 1123–1131.PubMed

69.

Gabrilovich, D., Ishida, T., Oyama, T., Ran, S., Kravtsov, V., Nadaf, S., et al. (1998). Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood, 92, 4150–4166.PubMed

70.

Ohm, J. E., & Carbone, D. P. (2001). VEGF as a mediator of tumor-associated immunodeficiency. Immunologic Research, 23, 263–272.PubMed

71.

Shojaei, F., Wu, X., Zhong, C., Yu, L., Liang, X. H., Yao, J., et al. (2007). Bv8 regulates myeloid-cell-dependent tumour angiogenesis. Nature, 450, 825–831.PubMed

72.

Pan, P. Y., Wang, G. X., Yin, B., Ozao, J., Ku, T., Divino, C. M., et al. (2008). Reversion of immune tolerance in advanced malignancy: Modulation of myeloid-derived suppressor cell development by blockade of stem-cell factor function. Blood, 111, 219–228.PubMed

73.

Curti, A., Fogli, M., Ratta, M., Tura, S., & Lemoli, R. M. (2001). Stem cell factor and FLT3-ligand are strictly required to sustain the long-term expansion of primitive CD34+DR- dendritic cell precursors. Journal of Immunology, 166, 848–854.

74.

Filipazzi, P., Valenti, R., Huber, V., Pilla, L., Canese, P., Iero, M., et al. (2007). Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. Journal of Clinical Oncology, 25, 2546–2553.PubMed

75.

Gabrilovich, D. I., & Nagaraj, S. (2009). Myeloid-derived suppressor cells as regulators of the immune system. Nature Reviews. Immunology, 9, 162–174.PubMed

76.

Serafini, P., Carbley, R., Noonan, K. A., Tan, G., Bronte, V., & Borrello, I. (2004). High-dose granulocyte-macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells. Cancer Research, 64, 6337–6343.PubMed

77.

Marigo, I., Dolcetti, L., Serafini, P., Zanovello, P., & Bronte, V. (2008). Tumor-induced tolerance and immune suppression by myeloid derived suppressor cells. Immunological Reviews, 222, 162–179.PubMed

78.

Costantino, L., & Barlocco, D. (2008). STAT 3 as a target for cancer drug discovery. Current Medicinal Chemistry, 15, 834–843.PubMed

79.

Kortylewski, M., Kujawski, M., Wang, T., Wei, S., Zhang, S., Pilon-Thomas, S., et al. (2005). Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Natural Medicines, 11, 1314–1321.

80.

Kortylewski, M., & Yu, H. (2008). Role of Stat3 in suppressing anti-tumor immunity. Current Opinion in Immunology, 20, 228–233.PubMed

81.

Yu, H., & Jove, R. (2004). The STATs of cancer—New molecular targets come of age. Nature Reviews. Cancer, 4, 97–105.PubMed

82.

Xie, T. X., Wei, D., Liu, M., Gao, A. C., Ali-Osman, F., Sawaya, R., et al. (2004). Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis. Oncogene, 23, 3550–3560.PubMed

83.

Noman, M. Z., Buart, S., Van Pelt, J., Richon, C., Hasmim, M., Leleu, N., et al. (2009). The cooperative induction of hypoxia-inducible factor-1alpha and STAT3 during hypoxia induced an impairment of tumor susceptibility to CTL-mediated cell lysis. Journal of Immunology, 182, 3510–3521.

84.

Kujawski, M., Kortylewski, M., Lee, H., Herrmann, A., Kay, H., & Yu, H. (2008). Stat3 mediates myeloid cell-dependent tumor angiogenesis in mice. The Journal of Clinical Investigation, 118, 3367–3377.PubMed

85.

Xin, H., Zhang, C., Herrmann, A., Du, Y., Figlin, R., & Yu, H. (2009). Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells. Cancer Research, 69, 2506–2513.PubMed

86.

Kim, D. W., Jo, Y. S., Jung, H. S., Chung, H. K., Song, J. H., Park, K. C., et al. (2006). An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases. The Journal of Clinical Endocrinology and Metabolism, 91, 4070–4076.PubMed

87.

Ozao-Choy, J., Ma, G., Kao, J., Wang, G. X., Meseck, M., Sung, M., et al. (2009). The novel role of tyrosine kinase inhibitor in the reversal of immune suppression and modulation of tumor microenvironment for immune-based cancer therapies. Cancer Research, 69, 2514–2522.PubMed

88.

Inman, B. A., Frigola, X., Dong, H., & Kwon, E. D. (2007). Costimulation, coinhibition and cancer. Current Cancer Drug Targets, 7, 15–30.PubMed

89.

Fox, S. B., Launchbury, R., Bates, G. J., Han, C., Shaida, N., Malone, P. R., et al. (2007). The number of regulatory T cells in prostate cancer is associated with the androgen receptor and hypoxia-inducible factor (HIF)-2alpha but not HIF-1alpha. The Prostate, 67, 623–629.PubMed

90.

Aghi, M., Cohen, K. S., Klein, R. J., Scadden, D. T., & Chiocca, E. A. (2006). Tumor stromal-derived factor-1 recruits vascular progenitors to mitotic neovasculature, where microenvironment influences their differentiated phenotypes. Cancer Research, 66, 9054–9064.PubMed

91.

Ben-Shoshan, J., Maysel-Auslender, S., Mor, A., Keren, G., & George, J. (2008). Hypoxia controls CD4+CD25+ regulatory T-cell homeostasis via hypoxia-inducible factor-1alpha. European Journal of Immunology, 38, 2412–2418.PubMed

92.

Dayan, F., Mazure, N. M., Brahimi-Horn, M. C., & Pouyssegur, J. (2008). A dialogue between the hypoxia-inducible factor and the tumor microenvironment. Cancer Microenviron, 1, 53–68.PubMed

93.

Sitkovsky, M. V., Kjaergaard, J., Lukashev, D., & Ohta, A. (2008). Hypoxia-adenosinergic immunosuppression: Tumor protection by T regulatory cells and cancerous tissue hypoxia. Clinical Cancer Research, 14, 5947–5952.PubMed

94.

Harizi, H., Juzan, M., Pitard, V., Moreau, J. F., & Gualde, N. (2002). Cyclooxygenase-2-issued prostaglandin e(2) enhances the production of endogenous IL-10, which down-regulates dendritic cell functions. Journal of Immunology, 168, 2255–2263.

95.

Baratelli, F., Lin, Y., Zhu, L., Yang, S. C., Heuze-Vourc’h, N., Zeng, G., et al. (2005). Prostaglandin E2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells. Journal of Immunology, 175, 1483–1490.

96.

Akasaki, Y., Liu, G., Chung, N. H., Ehtesham, M., Black, K. L., & Yu, J. S. (2004). Induction of a CD4+ T regulatory type 1 response by cyclooxygenase-2-overexpressing glioma. Journal of Immunology, 173, 4352–4359.

97.

Bergmann, C., Strauss, L., Zeidler, R., Lang, S., & Whiteside, T. L. (2007). Expansion of human T regulatory type 1 cells in the microenvironment of cyclooxygenase 2 overexpressing head and neck squamous cell carcinoma. Cancer Research, 67, 8865–8873.PubMed

98.

Rodriguez, P. C., Hernandez, C. P., Quiceno, D., Dubinett, S. M., Zabaleta, J., Ochoa, J. B., et al. (2005). Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma. The Journal of Experimental Medicine, 202, 931–939.PubMed

99.

Murakami, A., & Ohigashi, H. (2007). Targeting NOX, INOS and COX-2 in inflammatory cells: Chemoprevention using food phytochemicals. International Journal of Cancer, 121, 2357–2363.

100.

Gately, S., & Li, W. W. (2004). Multiple roles of COX-2 in tumor angiogenesis: A target for antiangiogenic therapy. Seminars in Oncology, 31, 2–11.PubMed

101.

Sharma, S., Yang, S. C., Zhu, L., Reckamp, K., Gardner, B., Baratelli, F., et al. (2005). Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression and CD4+ CD25+ T regulatory cell activities in lung cancer. Cancer Research, 65, 5211–5220.PubMed

102.

Haas, A. R., Sun, J., Vachani, A., Wallace, A. F., Silverberg, M., Kapoor, V., et al. (2006). Cycloxygenase-2 inhibition augments the efficacy of a cancer vaccine. Clinical Cancer Research, 12, 214–222.PubMed

103.

Greenhough, A., Smartt, H. J., Moore, A. E., Roberts, H. R., Williams, A. C., Paraskeva, C., et al. (2009). The COX-2/PGE2 pathway: Key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis, 30, 377–386.PubMed

104.

Motzer, R. J., Michaelson, M. D., Redman, B. G., Hudes, G. R., Wilding, G., Figlin, R. A., et al. (2006). Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. Journal of Clinical Oncology, 24, 16–24.PubMed

105.

Norden-Zfoni, A., Desai, J., Manola, J., Beaudry, P., Force, J., Maki, R., et al. (2007). Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor. Clinical Cancer Research, 13, 2643–2650.PubMed

106.

Dellapasqua, S., Bertolini, F., Bagnardi, V., Campagnoli, E., Scarano, E., Torrisi, R., et al. (2008). Metronomic cyclophosphamide and capecitabine combined with bevacizumab in advanced breast cancer. Journal of Clinical Oncology, 26, 4899–4905.PubMed

107.

Bertolini, F., Shaked, Y., Mancuso, P., & Kerbel, R. S. (2006). The multifaceted circulating endothelial cell in cancer: Towards marker and target identification. Nature Reviews. Cancer, 6, 835–845.PubMed

108.

Farace, F., Massard, C., Borghi, E., Bidart, J. M., & Soria, J. C. (2007). Vascular disrupting therapy-induced mobilization of circulating endothelial progenitor cells. Annals of Oncology, 18, 1421–1422.PubMed

109.

Ebos, J. M., Lee, C. R., Christensen, J. G., Mutsaers, A. J., & Kerbel, R. S. (2007). Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy. Proceedings of the National Academy of Sciences of the United States of America, 104, 17069–17074.PubMed

110.

Brown, A. P., Citrin, D. E., & Camphausen, K. A. (2008). Clinical biomarkers of angiogenesis inhibition. Cancer and Metastasis Reviews, 27, 415–434.PubMed

111.

Rini, B. I., Michaelson, M. D., Rosenberg, J. E., Bukowski, R. M., Sosman, J. A., Stadler, W. M., et al. (2008). Antitumor activity and biomarker analysis of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma. Journal of Clinical Oncology, 26, 3743–3748.PubMed

112.

Prior, J. O., Montemurro, M., Orcurto, M. V., Michielin, O., Luthi, F., Benhattar, J., et al. (2009). Early prediction of response to sunitinib after imatinib failure by 18F-fluorodeoxyglucose positron emission tomography in patients with gastrointestinal stromal tumor. Journal of Clinical Oncology, 27, 439–445.PubMed

113.

Michael, A., Relph, K., & Pandha, H. (2010). Emergence of potential biomarkers of response to anti-angiogenic anti-tumour agents. International Journal of Cancer, 127, 1251–1258.

114.

Lamuraglia, M., Escudier, B., Chami, L., Schwartz, B., Leclere, J., Roche, A., et al. (2006). To predict progression-free survival and overall survival in metastatic renal cancer treated with sorafenib: Pilot study using dynamic contrast-enhanced Doppler ultrasound. European Journal of Cancer, 42, 2472–2479.PubMed

115.

Fournier, L. S., Oudard, S., Thiam, R., Trinquart, L., Banu, E., Medioni, J., et al. (2010). Metastatic renal carcinoma: Evaluation of antiangiogenic therapy with dynamic contrast-enhanced CT. Radiology, 256, 511–518.PubMed

116.

Thiam, R., Fournier, L. S., Trinquart, L., Medioni, J., Chatellier, G., Balvay, D., et al. (2010). Optimizing the size variation threshold for the CT evaluation of response in metastatic renal cell carcinoma treated with sunitinib. Annals of Oncology, 21, 936–941.PubMed

117.

Escudier, B., Pluzanska, A., Koralewski, P., Ravaud, A., Bracarda, S., Szczylik, C., et al. (2007). Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: A randomised, double-blind phase III trial. Lancet, 370, 2103–2111.PubMed

118.

Rixe, O., Bukowski, R. M., Michaelson, M. D., Wilding, G., Hudes, G. R., Bolte, O., et al. (2007). Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: A phase II study. The Lancet Oncology, 8, 975–984.PubMed

119.

Yang, J. C., Haworth, L., Sherry, R. M., Hwu, P., Schwartzentruber, D. J., Topalian, S. L., et al. (2003). A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. The New England Journal of Medicine, 349, 427–434.PubMed

120.

Faivre, S., Delbaldo, C., Vera, K., Robert, C., Lozahic, S., Lassau, N., et al. (2006). Safety, pharmacokinetic, and antitumor activity of SU11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. Journal of Clinical Oncology, 24, 25–35.PubMed

121.

van Cruijsen, H., van der Veldt, A. A., Vroling, L., Oosterhoff, D., Broxterman, H. J., Scheper, R. J., et al. (2008). Sunitinib-induced myeloid lineage redistribution in renal cell cancer patients: CD1c+ dendritic cell frequency predicts progression-free survival. Clinical Cancer Research, 14, 5884–5892.PubMed

122.

George, S., Richmond, A., Elson, P., Jin, T., Wood, L., Garcia, J. A., et al. (2007). WBC changes as a pharmacodynamic marker of outcome in metastatic renal cell carcinoma (mRCC) patients (Pts) receiving sunitinib (p. 5043). Chicago: ASCO.

123.

Griffiths, R. W., Elkord, E., Gilham, D. E., Ramani, V., Clarke, N., Stern, P. L., et al. (2007). Frequency of regulatory T cells in renal cell carcinoma patients and investigation of correlation with survival. Cancer Immunology, Immunotherapy, 56, 1743–1753.PubMed

124.

Shojaei, F., Wu, X., Malik, A. K., Zhong, C., Baldwin, M. E., Schanz, S., et al. (2007). Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nature Biotechnology, 25, 911–920.PubMed

125.

Huang, D., Ding, Y., Zhou, M., Rini, B. I., Petillo, D., Qian, C. N., et al. (2010). Interleukin-8 mediates resistance to antiangiogenic agent sunitinib in renal cell carcinoma. Cancer Research, 70, 1063–1071.PubMed

126.

Nikolinakos, P. G., Altorki, N., Yankelevitz, D., Tran, H. T., Yan, S., Rajagopalan, D., et al. (2010). Plasma cytokine and angiogenic factor profiling identifies markers associated with tumor shrinkage in early-stage non-small cell lung cancer patients treated with pazopanib. Cancer Research, 70, 2171–2179.PubMed

127.

Hanrahan, E. O., Lin, H. Y., Kim, E. S., Yan, S., Du, D. Z., McKee, K. S., et al. (2010). Distinct patterns of cytokine and angiogenic factor modulation and markers of benefit for vandetanib and/or chemotherapy in patients with non-small-cell lung cancer. Journal of Clinical Oncology, 28, 193–201.PubMed

128.

Tartour, E., Mosseri, V., Jouffroy, T., Deneux, L., Jaulerry, C., Brunin, F., et al. (2001). Serum soluble interleukin-2 receptor concentrations as an independent prognostic marker in head and neck cancer. Lancet, 357, 1263–1264.PubMed

129.

Tartour, E., Deneux, L., Mosseri, V., Jaulerry, C., Brunin, F., Point, D., et al. (1997). Soluble interleukin-2 receptor serum level as a predictor of locoregional control and survival for patients with head and neck carcinoma: Results of a multivariate prospective study. Cancer, 79, 1401–1408.PubMed

130.

Saltz, L. B., Rosen, L. S., Marshall, J. L., Belt, R. J., Hurwitz, H. I., Eckhardt, S. G., et al. (2007). Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy. Journal of Clinical Oncology, 25, 4793–4799.PubMed

131.

Bergers, G., & Hanahan, D. (2008). Modes of resistance to anti-angiogenic therapy. Nature Reviews. Cancer, 8, 592–603.PubMed

132.

Willett, C. G., Boucher, Y., di Tomaso, E., Duda, D. G., Munn, L. L., Tong, R. T., et al. (2004). Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Natural Medicines, 10, 145–147.

133.

Hamzah, J., Jugold, M., Kiessling, F., Rigby, P., Manzur, M., Marti, H. H., et al. (2008). Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature, 453, 410–414.PubMed

134.

Dirkx, A. E., oude Egbrink, M. G., Castermans, K., van der Schaft, D. W., Thijssen, V. L., Dings, R. P., et al. (2006). Anti-angiogenesis therapy can overcome endothelial cell anergy and promote leukocyte-endothelium interactions and infiltration in tumors. FASEB Journal, 20, 621–630.PubMed

135.

Li, B., Lalani, A. S., Harding, T. C., Luan, B., Koprivnikar, K., Huan Tu, G., et al. (2006). Vascular endothelial growth factor blockade reduces intratumoral regulatory T cells and enhances the efficacy of a GM-CSF-secreting cancer immunotherapy. Clinical Cancer Research, 12, 6808–6816.PubMed

136.

Manning, E. A., Ullman, J. G., Leatherman, J. M., Asquith, J. M., Hansen, T. R., Armstrong, T. D., et al. (2007). A vascular endothelial growth factor receptor-2 inhibitor enhances antitumor immunity through an immune-based mechanism. Clinical Cancer Research, 13, 3951–3959.PubMed

137.

Shrimali, R. K., Yu, Z., Theoret, M. R., Chinnasamy, D., Restifo, N. P., & Rosenberg, S. A. (2010). Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer. Cancer Research, 70, 6171–6180.PubMed

138.

Nair, S., Boczkowski, D., Moeller, B., Dewhirst, M., Vieweg, J., & Gilboa, E. (2003). Synergy between tumor immunotherapy and antiangiogenic therapy. Blood, 102, 964–971.PubMed

139.

Bercovici, N., Haicheur, N., Massicard, S., Vernel-Pauillac, F., Adotevi, O., Landais, D., et al. (2008). Analysis and characterization of antitumor T-cell response after administration of dendritic cells loaded with allogeneic tumor lysate to metastatic melanoma patients. Journal of Immunotherapy, 31, 101–112.PubMed

140.

Huang, K. W., Wu, H. L., Lin, H. L., Liang, P. C., Chen, P. J., Chen, S. H., et al. (2010). Combining antiangiogenic therapy with immunotherapy exerts better therapeutical effects on large tumors in a woodchuck hepatoma model. Proceedings of the National Academy of Sciences of the United States of America, 107, 14769–14774.PubMed

141.

Kerzerho, J., Adotevi, O., Castelli, F. A., Dosset, M., Bernardeau, K., Szely, N., et al. (2010). The angiogenic growth factor and biomarker midkine is a tumor-shared antigen. Journal of Immunology, 185, 418–423.

142.

Molhoek, K. R., McSkimming, C. C., Olson, W. C., Brautigan, D. L., & Slingluff, C. L., Jr. (2009). Apoptosis of CD4(+)CD25(high) T cells in response to Sirolimus requires activation of T cell receptor and is modulated by IL-2. Cancer Immunology, Immunotherapy, 58, 867–876.PubMed

143.

Albini, A., Brigati, C., Ventura, A., Lorusso, G., Pinter, M., Morini, M., et al. (2009). Angiostatin anti-angiogenesis requires IL-12: The innate immune system as a key target. Journal of Translational Medicine, 7, 5.PubMed

144.

Rini, B. I., Halabi, S., Rosenberg, J. E., Stadler, W. M., Vaena, D. A., Ou, S. S., et al. (2008). Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. Journal of Clinical Oncology, 26, 5422–5428.PubMed

145.

Flaherty, K. T. (2010). Where does the combination of sorafenib and interferon in renal cell carcinoma stand? Cancer, 116, 4–7.PubMed

146.

Zhao, W., Gu, Y. H., Song, R., Qu, B. Q., & Xu, Q. (2008). Sorafenib inhibits activation of human peripheral blood T cells by targeting LCK phosphorylation. Leukemia, 22, 1226–1233.PubMed

147.

Houben, R., Voigt, H., Noelke, C., Hofmeister, V., Becker, J. C., & Schrama, D. (2009). MAPK-independent impairment of T-cell responses by the multikinase inhibitor sorafenib. Molecular Cancer Therapeutics, 8, 433–440.PubMed

Title: Angiogenesis and immunity: a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy
Authors: Eric Tartour
H. Pere
B. Maillere
M. Terme
N. Merillon
J. Taieb
F. Sandoval
F. Quintin-Colonna
K. Lacerda
A. Karadimou
C. Badoual
A. Tedgui
W. H. Fridman
S. Oudard
Publication date: 01-03-2011
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 1/2011
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-011-9281-4

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2011

Preface

The significant role of mast cells in cancer

Molecular determinants of immunogenic cell death elicited by anticancer chemotherapy

Improving cancer immunotherapy by targeting tumor-induced immune suppression

Modulation of tumor immunity by therapeutic monoclonal antibodies

Myeloid cell diversification and complexity: an old concept with new turns in oncology

Keynote webinar | Spotlight on antibody–drug conjugates in cancer