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Published in:

01-12-2009

The role of neutrophils and TNF-related apoptosis-inducing ligand (TRAIL) in bacillus Calmette–Guérin (BCG) immunotherapy for urothelial carcinoma of the bladder

Authors: Henry M. Rosevear, Andrew J. Lightfoot, Michael A. O’Donnell, Thomas S. Griffith

Published in: Cancer and Metastasis Reviews | Issue 3-4/2009

Abstract

Intravesical Mycobacterium bovis bacillus Calmette–Guérin (BCG) immunotherapy is a highly effective treatment for carcinoma in situ of the bladder, as well as high-risk nonmuscle invasive urothelial carcinoma of the bladder. Despite over 30 years of clinical experience with BCG, the therapy’s mechanism has remained enigmatic. Observations regarding the role of neutrophils in BCG immunotherapy have led to exciting discoveries regarding the potential role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in creating the therapeutic benefit of BCG immunotherapy. In this paper, we will review the scope of the disease, highlight our understanding of the role for BCG in urothelial carcinoma of the bladder, explain the recent discoveries regarding the role of neutrophils and TRAIL in therapy, and theorize on potential future areas of research.

Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., Murray, T., et al. (2008). Cancer statistics, 2008. CA: A Cancer Journal for Clinicians, 58, 71–96.CrossRef

Parkin, D. M. (2008). The global burden of urinary bladder cancer. Scandinavian Journal of Urology and Nephrology Supplementum, 42, 12–20.CrossRef

Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., & Thun, M. J. (2009). Cancer statistics, 2009. CA: A Cancer Journal for Clinicians, 59, 225–249.CrossRef

Vainio, H., Heseltine, E., & Wilbourn, J. (1994). Priorities for future IARC monographs on the evaluation of carcinogenic risks to humans. Environmental Health Perspectives, 102, 590–591.CrossRefPubMed

Kirkali, Z., Chan, T., Manoharan, M., Algaba, F., Busch, C., Cheng, L., et al. (2005). Bladder cancer: Epidemiology, staging and grading, and diagnosis. Urology, 66, 4–34.CrossRefPubMed

Lopez-Beltran, A., & Montironi, R. (2004). Non-invasive urothelial neoplasms: According to the most recent WHO classification. European Urology, 46, 170–176.CrossRefPubMed

Montironi, R., & Lopez-Beltran, A. (2005). The 2004 WHO classification of bladder tumors: A summary and commentary. International Journal of Surgical Pathology, 13, 143–153.CrossRefPubMed

Reuter, V. E. (2006). The pathology of bladder cancer. Urology, 67, 11–17. discussion 17–18.CrossRefPubMed

Pavone-Macaluso, M., Lopez-Beltran, A., Aragona, F., Bassi, P., & Fitzpatrick, J. M. (2006). The pathology of bladder cancer: An update on selected issues. BJU International, 98, 1161–1165.CrossRefPubMed

10.

Kretschmer, H. (1925). Haematuria: A clinical study based on 933 consecutive cases. Surgery, Gynecology and Obstetrics, 40, 683–686.

11.

Montironi, R., Mazzucchelli, R., Scarpelli, M., Lopez-Beltran, A., & Cheng, L. (2008). Morphological diagnosis of urothelial neoplasms. Journal of Clinical Pathology, 61, 3–10.CrossRefPubMed

12.

Eble, J. (2004). World health organization classification of tumors: Pathology and genetics of tumors of the urinary system and male genital organs. Lyons: IARC.

13.

Klein, E. A., et al. (2007). Epidemiology, etiology, and prevention of prostate cancer. In A. J. Wein, et al. (Eds.), Campbell-Walsh urology. Philadelphia: Saunders.

14.

Droller, M. J. (1998). Bladder cancer: State-of-the-art care. CA: A Cancer Journal for Clinicians, 48, 269–284.CrossRef

15.

Kaye, K. W., & Lange, P. H. (1982). Mode of presentation of invasive bladder cancer: Reassessment of the problem. Journal of Urology, 128, 31–33.PubMed

16.

Kemp, T. J., Ludwig, A. T., Earel, J. K., Moore, J. M., Vanoosten, R. L., Moses, B., et al. (2005). Neutrophil stimulation with Mycobacterium bovis bacillus Calmette–Guerin (BCG) results in the release of functional soluble TRAIL/Apo-2L. Blood, 106, 3474–3482.CrossRefPubMed

17.

Botteman, M. F., Pashos, C. L., Redaelli, A., Laskin, B., & Hauser, R. (2003). The health economics of bladder cancer: A comprehensive review of the published literature. Pharmacoeconomics, 21, 1315–1330.CrossRefPubMed

18.

Hollenbeck, B. K., Ye, Z., Dunn, R. L., Montie, J. E., & Birkmeyer, J. D. (2009). Provider treatment intensity and outcomes for patients with early-stage bladder cancer. Journal of the National Cancer Institute, 101, 571–580.CrossRefPubMed

19.

Morales, A., Eidinger, D., & Bruce, A. W. (1976). Intracavitary bacillus Calmette–Guerin in the treatment of superficial bladder tumors. Journal of Urology, 116, 180–183.PubMed

20.

Belldegrun, A. S., Franklin, J. R., O'Donnell, M. A., Gomella, L. G., Klein, E., Neri, R., et al. (1998). Superficial bladder cancer: The role of interferon-alpha. Journal of Urology, 159, 1793–1801.CrossRefPubMed

21.

Weiss, G. R., O'Donnell, M. A., Loughlin, K., Zonno, K., Laliberte, R. J., & Sherman, M. L. (2003). Phase 1 study of the intravesical administration of recombinant human interleukin-12 in patients with recurrent superficial transitional cell carcinoma of the bladder. Journal of Immunotherapy, 26, 343–348.CrossRefPubMed

22.

Joudi, F. N., Smith, B. J., & O'Donnell, M. A. (2006). Final results from a national multicenter phase II trial of combination bacillus Calmette–Guerin plus interferon alpha-2B for reducing recurrence of superficial bladder cancer. Urologic Oncology, 24, 344–348.PubMed

23.

Babjuk, M., Oosterlinck, W., Sylvester, R., Kaasinen, E., Bohle, A., & Palou-Redorta, J. (2008). EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder. European Urology, 54, 303–314.CrossRefPubMed

24.

Herr, H. W., Laudone, V. P., Badalament, R. A., Oettgen, H. F., Sogani, P. C., Freedman, B. D., et al. (1988). Bacillus Calmette–Guerin therapy alters the progression of superficial bladder cancer. Journal of Clinical Oncology, 6, 1450–1455.PubMed

25.

Pawinski, A., Sylvester, R., Kurth, K. H., Bouffioux, C., van der Meijden, A., Parmar, M. K., et al. (1996). A combined analysis of European organization for research and treatment of cancer, and medical research council randomized clinical trials for the prophylactic treatment of stage TaT1 bladder cancer. European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council Working Party on Superficial Bladder Cancer. Journal of Urology, 156, 1934–1940. discussion 1940–1931.CrossRefPubMed

26.

Sylvester, R. J., van der Meijden, A. P., Witjes, J. A., & Kurth, K. (2005). Bacillus Calmette–Guerin versus chemotherapy for the intravesical treatment of patients with carcinoma in situ of the bladder: A meta-analysis of the published results of randomized clinical trials. Journal of Urology, 174, 86–91. discussion 91–82.CrossRefPubMed

27.

Herr, H. W., Schwalb, D. M., Zhang, Z. F., Sogani, P. C., Fair, W. R., Whitmore, W. F., Jr., et al. (1995). Intravesical bacillus Calmette–Guerin therapy prevents tumor progression and death from superficial bladder cancer: Ten-year follow-up of a prospective randomized trial. Journal of Clinical Oncology, 13, 1404–1408.PubMed

28.

Hall, M. C., Chang, S. S., Dalbagni, G., Pruthi, R. S., Seigne, J. D., Skinner, E. C., et al. (2007). Guideline for the management of nonmuscle invasive bladder cancer (stages Ta, T1, and Tis): 2007 update. Journal of Urology, 178, 2314–2330.CrossRefPubMed

29.

Spiess, P. E., & Grossman, H. B. (2006). Fluorescence cystoscopy: Is it ready for use in routine clinical practice? Current Opinion in Urology, 16, 372–376.CrossRefPubMed

30.

Kriegmair, M., Baumgartner, R., Knuchel, R., Stepp, H., Hofstadter, F., & Hofstetter, A. (1996). Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence. Journal of Urology, 155, 105–109. discussion 109–110.CrossRefPubMed

31.

Lamm, D. L. (1992). Long-term results of intravesical therapy for superficial bladder cancer. Urologic Clinics of North America, 19, 573–580.PubMed

32.

Bohle, A., Jocham, D., & Bock, P. R. (2003). Intravesical bacillus Calmette–Guerin versus mitomycin C for superficial bladder cancer: A formal meta-analysis of comparative studies on recurrence and toxicity. Journal of Urology, 169, 90–95.CrossRefPubMed

33.

Lamm, D. L., van der Meijden, P. M., Morales, A., Brosman, S. A., Catalona, W. J., Herr, H. W., et al. (1992). Incidence and treatment of complications of bacillus Calmette–Guerin intravesical therapy in superficial bladder cancer. Journal of Urology, 147, 596–600.PubMed

34.

Bhan, R., Pisharodi, L. R., Gudlaugsson, E., & Bedrossian, C. (1998). Cytological, histological, and clinical correlations in intravesical bacillus Calmette–Guerin immunotherapy. Annals of Diagnostic Pathology, 2, 55–60.CrossRefPubMed

35.

Anonymous. (1998). Case records of the Massachusetts General Hospital Weekly Clinicopathological exercises Case 29. New England Journal of Medicine, 339, 831.

36.

Elkabani, M., Greene, J. N., Vincent, A. L., VanHook, S., & Sandin, R. L. (2000). Disseminated Mycobacterium bovis after intravesicular bacillus Calmette–Guérin treatments for bladder cancer. Cancer Control: Journal of the Moffitt Cancer Center, 7, 476–481.

37.

Nadasy, K. A., Patel, R. S., Emmett, M., Murillo, R. A., Tribble, M. A., Black, R. D., et al. (2008). Four cases of disseminated Mycobacterium bovis infection following intravesical BCG instillation for treatment of bladder carcinoma. Southern Medical Journal, 101, 91–95.PubMed

38.

Saint, F., Patard, J. J., Irani, J., Salomon, L., Hoznek, A., Legrand, P., et al. (2001). Leukocyturia as a predictor of tolerance and efficacy of intravesical BCG maintenance therapy for superficial bladder cancer. Urology, 57, 617–621. discussion 621–612.CrossRefPubMed

39.

Torrence, R. J., Kavoussi, L. R., Catalona, W. J., & Ratliff, T. L. (1988). Prognostic factors in patients treated with intravesical bacillus Calmette–Guerin for superficial bladder cancer. Journal of Urology, 139, 941–944.PubMed

40.

Watanabe, E., Matsuyama, H., Matsuda, K., Ohmi, C., Tei, Y., Yoshihiro, S., et al. (2003). Urinary interleukin-2 may predict clinical outcome of intravesical bacillus Calmette–Guerin immunotherapy for carcinoma in situ of the bladder. Cancer Immunology and Immunotherapy, 52, 481–486.CrossRefPubMed

41.

Saint, F., Patard, J. J., Maille, P., Soyeux, P., Hoznek, A., Salomon, L., et al. (2002). Prognostic value of a T helper 1 urinary cytokine response after intravesical bacillus Calmette–Guerin treatment for superficial bladder cancer. Journal of Urology, 167, 364–367.CrossRefPubMed

42.

Shintani, Y., Sawada, Y., Inagaki, T., Kohjimoto, Y., Uekado, Y., & Shinka, T. (2007). Intravesical instillation therapy with bacillus Calmette–Guerin for superficial bladder cancer: Study of the mechanism of bacillus Calmette–Guerin immunotherapy. International Journal of Urology, 14, 140–146.CrossRefPubMed

43.

Yarbro, C., Frogge, M., & Goodman, M. (2006). Cancer nursing: Principles and practice, 6th edn. Sudburry, Massachusetts: Jones and Bartlett Publishers.

44.

Ludwig, A. T., Moore, J. M., Luo, Y., Chen, X., Saltsgaver, N. A., O'Donnell, M. A., et al. (2004). Tumor necrosis factor-related apoptosis-inducing ligand: A novel mechanism for bacillus Calmette–Guerin-induced antitumor activity. Cancer Research, 64, 3386–3390.CrossRefPubMed

45.

Zhao, W., Schorey, J. S., Groger, R., Allen, P. M., Brown, E. J., & Ratliff, T. L. (1999). Characterization of the fibronectin binding motif for a unique mycobacterial fibronectin attachment protein, FAP. Journal of Biological Chemistry, 274, 4521–4526.CrossRefPubMed

46.

Kavoussi, L. R., Brown, E. J., Ritchey, J. K., & Ratliff, T. L. (1990). Fibronectin-mediated Calmette–Guerin bacillus attachment to murine bladder mucosa. Requirement for the expression of an antitumor response. Journal of Clinical Investigation, 85, 62–67.CrossRefPubMed

47.

Becich, M. J., Carroll, S., & Ratliff, T. L. (1991). Internalization of bacille Calmette–Guerin by bladder tumor cells. Journal of Urology, 145, 1316–1324.PubMed

48.

Luo, Y., Szilvasi, A., Chen, X., DeWolf, W. C., & O'Donnell, M. A. (1996). A novel method for monitoring Mycobacterium bovis BCG trafficking with recombinant BCG expressing green fluorescent protein. Clinical and Diagnostic Laboratory Immunology, 3, 761–768.PubMed

49.

Schamhart, D. H., de Boer, E. C., de Reijke, T. M., & Kurth, K. (2000). Urinary cytokines reflecting the immunological response in the urinary bladder to biological response modifiers: Their practical use. European Urology, 37(Suppl 3), 16–23.CrossRefPubMed

50.

Thalmann, G. N., Sermier, A., Rentsch, C., Mohrle, K., Cecchini, M. G., & Studer, U. E. (2000). Urinary interleukin-8 and 18 predict the response of superficial bladder cancer to intravesical therapy with bacillus Calmette–Guerin. Journal of Urology, 164, 2129–2133.CrossRefPubMed

51.

de Boer, E. C., de Jong, W. H., van der Meijden, A. P., Steerenberg, P. A., Witjes, F., Vegt, P. D., et al. (1991). Leukocytes in the urine after intravesical BCG treatment for superficial bladder cancer. A flow cytofluorometric analysis. Urologic Research, 19, 45–50.CrossRef

52.

de Reijke, T. M., de Boer, E. C., Kurth, K. H., & Schamhart, D. H. (1996). Urinary cytokines during intravesical bacillus Calmette–Guerin therapy for superficial bladder cancer: Processing, stability and prognostic value. Journal of Urology, 155, 477–482.CrossRefPubMed

53.

Bohle, A., Nowc, C., Ulmer, A. J., Musehold, J., Gerdes, J., Hofstetter, A. G., et al. (1990). Elevations of cytokines interleukin-1, interleukin-2 and tumor necrosis factor in the urine of patients after intravesical bacillus Calmette–Guerin immunotherapy. Journal of Urology, 144, 59–64.PubMed

54.

Jackson, A. M., Alexandroff, A. B., Kelly, R. W., Skibinska, A., Esuvaranathan, K., Prescott, S., et al. (1995). Changes in urinary cytokines and soluble intercellular adhesion molecule-1 (ICAM-1) in bladder cancer patients after bacillus Calmette–Guerin (BCG) immunotherapy. Clinical and Experimental Immunology, 99, 369–375.PubMedCrossRef

55.

Luo, Y., Chen, X., Downs, T. M., DeWolf, W. C., & O'Donnell, M. A. (1999). IFN-alpha 2B enhances Th1 cytokine responses in bladder cancer patients receiving Mycobacterium bovis bacillus Calmette–Guerin immunotherapy. Journal of Immunology, 162, 2399–2405.

56.

Armitage, R. J. (1994). Tumor necrosis factor receptor superfamily members and their ligands. Current Opinion in Immunology, 6, 407–413.CrossRefPubMed

57.

Martinez-Lorenzo, M. J., Alava, M. A., Gamen, S., Kim, K. J., Chuntharapai, A., Pineiro, A., et al. (1998). Involvement of APO2 ligand/TRAIL in activation-induced death of Jurkat and human peripheral blood T cells. European Journal of Immunology, 28, 2714–2725.CrossRefPubMed

58.

Cha, S. S., Kim, M. S., Choi, Y. H., Sung, B. J., Shin, N. K., Shin, H. C., et al. (1999). 2.8 A resolution crystal structure of human TRAIL, a cytokine with selective antitumor activity. Immunity, 11, 253–261.CrossRefPubMed

59.

Hymowitz, S. G., Christinger, H. W., Fuh, G., Ultsch, M., O'Connell, M., Kelley, R. F., et al. (1999). Triggering cell death: The crystal structure of Apo2L/TRAIL in a complex with death receptor 5. Molecular Cell, 4, 563–571.CrossRefPubMed

60.

Hymowitz, S. G., O'Connell, M. P., Ultsch, M. H., Hurst, A., Totpal, K., Ashkenazi, A., et al. (2000). A unique zinc-binding site revealed by a high-resolution X-ray structure of homotrimeric Apo2L/TRAIL. Biochemistry, 39, 633–640.CrossRefPubMed

61.

Bodmer, J. L., Meier, P., Tschopp, J., & Schneider, P. (2000). Cysteine 230 is essential for the structure and activity of the cytotoxic ligand TRAIL. Journal of Biological Chemistry, 275, 20632–20637.CrossRefPubMed

62.

Wiley, S. R., Schooley, K., Smolak, P. J., Din, W. S., Huang, C. P., Nicholl, J. K., et al. (1995). Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity, 3, 673–682.CrossRefPubMed

63.

Pitti, R. M., Marsters, S. A., Ruppert, S., Donahue, C. J., Moore, A., & Ashkenazi, A. (1996). Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. Journal of Biological Chemistry, 271, 12687–12690.CrossRefPubMed

64.

Griffith, T. S., Chin, W. A., Jackson, G. C., Lynch, D. H., & Kubin, M. Z. (1998). Intracellular regulation of TRAIL-induced apoptosis in human melanoma cells. Journal of Immunology, 161, 2833–2840.

65.

Griffith, T. S., Rauch, C. T., Smolak, P. J., Waugh, J. Y., Boiani, N., Lynch, D. H., et al. (1999). Functional analysis of TRAIL receptors using monoclonal antibodies. Journal of Immunology, 162, 2597–2605.

66.

Degli-Esposti, M. A., Dougall, W. C., Smolak, P. J., Waugh, J. Y., Smith, C. A., & Goodwin, R. G. (1997). The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Immunity, 7, 813–820.CrossRefPubMed

67.

Griffith, T. S., & Lynch, D. H. (1998). TRAIL: A molecule with multiple receptors and control mechanisms. Current Opinion in Immunology, 10, 559–563.CrossRefPubMed

68.

Emery, J. G., McDonnell, P., Burke, M. B., Deen, K. C., Lyn, S., Silverman, C., et al. (1998). Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. Journal of Biological Chemistry, 273, 14363–14367.CrossRefPubMed

69.

Walczak, H., Degli-Esposti, M. A., Johnson, R. S., Smolak, P. J., Waugh, J. Y., Boiani, N., et al. (1997). TRAIL-R2: A novel apoptosis-mediating receptor for TRAIL. EMBO Journal, 16, 5386–5397.CrossRefPubMed

70.

Pang, A. S., & Morales, A. (1982). BCG induced murine peritoneal exudate cells: Cytotoxic activity against a syngeneic bladder tumor cell line. Journal of Urology, 127, 1225–1229.PubMed

71.

Song, K., Chen, Y., Goke, R., Wilmen, A., Seidel, C., Goke, A., et al. (2000). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an inhibitor of autoimmune inflammation and cell cycle progression. Journal of Experimental Medicine, 191, 1095–1104.CrossRefPubMed

72.

Lamhamedi-Cherradi, S. E., Zheng, S. J., Maguschak, K. A., Peschon, J., & Chen, Y. H. (2003). Defective thymocyte apoptosis and accelerated autoimmune diseases in TRAIL−/− mice. Nature Immunology, 4, 255–260.CrossRefPubMed

73.

Mi, Q. S., Ly, D., Lamhamedi-Cherradi, S. E., Salojin, K. V., Zhou, L., Grattan, M., et al. (2003). Blockade of tumor necrosis factor-related apoptosis-inducing ligand exacerbates type 1 diabetes in NOD mice. Diabetes, 52, 1967–1975.CrossRefPubMed

74.

Lamhamedi-Cherradi, S. E., Zheng, S., Tisch, R. M., & Chen, Y. H. (2003). Critical roles of tumor necrosis factor-related apoptosis-inducing ligand in type 1 diabetes. Diabetes, 52, 2274–2278.CrossRefPubMed

75.

Brown, A. E., Holzer, T. J., & Andersen, B. R. (1987). Capacity of human neutrophils to kill mycobacterium tuberculosis. Journal of Infectious Disease, 156, 985–989.

76.

Fulton, S. A., Reba, S. M., Martin, T. D., & Boom, W. H. (2002). Neutrophil-mediated mycobacteriocidal immunity in the lung during Mycobacterium bovis BCG infection in C57BL/6 mice. Infection and Immunity, 70, 5322–5327.CrossRefPubMed

77.

Appelberg, R., Castro, A. G., Gomes, S., Pedrosa, J., & Silva, M. T. (1995). Susceptibility of beige mice to mycobacterium avium: Role of neutrophils. Infection and Immunity, 63, 3381–3387.PubMed

78.

Koga, Y., Matsuzaki, A., Suminoe, A., Hattori, H., & Hara, T. (2004). Neutrophil-derived TNF-related apoptosis-inducing ligand (TRAIL): A novel mechanism of antitumor effect by neutrophils. Cancer Research, 64, 1037–1043.CrossRefPubMed

79.

Kamohara, H., Matsuyama, W., Shimozato, O., Abe, K., Galligan, C., Hashimoto, S., et al. (2004). Regulation of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor expression in human neutrophils. Immunology, 111, 186–194.CrossRefPubMed

80.

Bisiaux, A., Thiounn, N., Timsit, M. O., Eladaoui, A., Chang, H. H., Mapes, J., et al. (2009). Molecular analyte profiling of the early events and tissue conditioning following intravesical bacillus Calmette–Guerin therapy in patients with superficial bladder cancer. Journal of Urology, 181, 1571–1580.CrossRefPubMed

81.

Alexandroff, A. B., Jackson, A. M., O'Donnell, M. A., & James, K. (1999). BCG immunotherapy of bladder cancer: 20 years on. Lancet, 353, 1689–1694.CrossRefPubMed

82.

Simons, M. P., Moore, J. M., Kemp, T. J., & Griffith, T. S. (2007). Identification of the mycobacterial subcomponents involved in the release of tumor necrosis factor-related apoptosis-inducing ligand from human neutrophils. Infection and Immunity, 75, 1265–1271.CrossRefPubMed

83.

Jones, B. W., Means, T. K., Heldwein, K. A., Keen, M. A., Hill, P. J., Belisle, J. T., et al. (2001). Different Toll-like receptor agonists induce distinct macrophage responses. Journal of Leukocyte Biology, 69, 1036–1044.PubMed

84.

Suttmann, H., Riemensberger, J., Bentien, G., Schmaltz, D., Stockle, M., Jocham, D., et al. (2006). Neutrophil granulocytes are required for effective bacillus Calmette–Guerin immunotherapy of bladder cancer and orchestrate local immune responses. Cancer Research, 66, 8250–8257.CrossRefPubMed

Title: The role of neutrophils and TNF-related apoptosis-inducing ligand (TRAIL) in bacillus Calmette–Guérin (BCG) immunotherapy for urothelial carcinoma of the bladder
Authors: Henry M. Rosevear
Andrew J. Lightfoot
Michael A. O’Donnell
Thomas S. Griffith
Publication date: 01-12-2009
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 3-4/2009
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-009-9195-6

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