Skip to main content
SpringerLink
Log in

Harnessing the Host Immune Response to Infection – BCG Immunotherapy for Bladder Cancer

  • Chapter
Infection and Cancer: Bi-Directorial Interactions

Abstract

Bacillus Calmette–Guérin, or BCG, an avirulent strain of Mycobacterium bovis, was developed as a vaccine for the prevention of tuberculosis. BCG’s success in disease prevention resulted in the vaccination of billions of individuals. The observation that bacterial components could induce tumor regression, coupled with reports that BCG-vaccinated individuals demonstrated reduced cancer incidence, led to the development of BCG as an immunotherapeutic agent. The pioneering work of Morales and colleagues in the 1970s, demonstrating that direct instillation of live BCG into the bladder of patients with nonmuscle invasive bladder cancer prevented tumor recurrence, laid the path for what is arguably the most successful immunotherapy to date. Notably, although much work has focused on how BCG mediates tumor immunity, important unknowns regarding the mechanism of action remain. Nonspecific innate pathways, such as neutrophil-mediated killing, and adaptive immunity, such as induction of BCG- and tumor-specific T cells, likely work in concert to exert anti-tumor effects. Finally, as the mechanisms of action are unraveled, questions of pharmaco-equivalency of BCG substrains have arisen with respect to the clinical management of bladder cancer patients. Thus, while BCG immunotherapy is currently the standard of care for nonmuscle invasive bladder cancer, there exists great opportunity to improve upon this treatment through additional research and clinical trials.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

BCG:

Bacillus Calmette–Guérin

FAP:

fibronectin attachment protein

IL:

interleukin

IFN:

interferon

NET:

neutrophil extracellular traps

TRAIL:

tumor necrosis factor-related apoptosis-inducing ligand

TUR:

transurethral resection

References

  • Andersen P, Doherty TM (2005) The success and failure of BCG – implications for a novel tuberculosis vaccine. Nat Rev Microbiol 3:656–662

    Article  CAS  PubMed  Google Scholar 

  • Arnaud C, Braunersreuther V, Mach F (2005) Toward immunomodulatory and anti-inflammatory properties of statins. Trends Cardiovasc Med 15:202–206

    Article  CAS  PubMed  Google Scholar 

  • BCG and cancer (1975). Can Med Assoc J 113(8):708–710

    Google Scholar 

  • Biot C et al (2012) Preexisting BCG-specific T cells improve intravesical immunotherapy for bladder cancer. Sci Transl Med 4:137ra172

    Article  CAS  Google Scholar 

  • Bisiaux A 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. J Urol 181:1571–1580

    Article  CAS  PubMed  Google Scholar 

  • Bloomberg SD, Brosman SA, Hausman MS, Cohen A, Battenberg JD (1975) The effects of BCG on the dog bladder. Investig Urol 12:423–427

    CAS  Google Scholar 

  • Boccafoschi C, Montefiore F, Pavesi M, Pastormerlo M, Betta PG (1995) Late effects of intravesical bacillus Calmette-Guerin immunotherapy on bladder mucosa infiltrating lymphocytes: an immunohistochemical study. Eur Urol 27:334–338

    CAS  PubMed  Google Scholar 

  • Bohle A 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. J Urol 144:59–64

    CAS  PubMed  Google Scholar 

  • Botteman MF, Pashos CL, Redaelli A, Laskin B, Hauser R (2003) The health economics of bladder cancer: a comprehensive review of the published literature. Pharmacoecon 21:1315–1330

    Article  Google Scholar 

  • Brandau S, Suttmann H (2007) Thirty years of BCG immunotherapy for non-muscle invasive bladder cancer: a success story with room for improvement. Biomed Pharmacother 61:299–305

    Article  CAS  PubMed  Google Scholar 

  • Breban R et al (2012) Mathematical model of tumor immunotherapy for bladder carcinoma identifies the limitations of the innate immune response. Oncoimmunol 1:9–17

    Article  Google Scholar 

  • Brinkmann V et al (2004) Neutrophil extracellular traps kill bacteria. Science 303:1532–1535

    Article  CAS  PubMed  Google Scholar 

  • Brosch R et al (2007) Genome plasticity of BCG and impact on vaccine efficacy. Proc Natl Acad Sci U S A 104:5596–5601

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chien YH, Zeng X, Prinz I (2013) The natural and the inducible: interleukin (IL)-17-producing gammadelta T cells. Trends Immunol 34:151–154

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cookson MS et al (1997) The treated natural history of high risk superficial bladder cancer: 15-year outcome. J Urol 158:62–67

    Article  CAS  PubMed  Google Scholar 

  • Cools-Lartigue J et al (2013) Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J Clin Invest. 2013 Aug 1; 123(8): 3446–3458

    Google Scholar 

  • Coxon A, Tang T, Mayadas TN (1999) Cytokine-activated endothelial cells delay neutrophil apoptosis in vitro and in vivo. A role for granulocyte/macrophage colony-stimulating factor. J Exp Med 190:923–934

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Czarnetzki BM et al (1993) Long-term adjuvant immunotherapy in stage I high risk malignant melanoma, comparing two BCG preparations versus non-treatment in a randomised multicentre study (EORTC Protocol 18781). Eur J Cancer 29A:1237–1242

    Article  CAS  PubMed  Google Scholar 

  • Daley JM, Thomay AA, Connolly MD, Reichner JS, Albina JE (2008) Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice. J Leukoc Biol 83:64–70

    Article  CAS  PubMed  Google Scholar 

  • Davignon L, Robillard P, Lemonde P, Frappier A (1970) B.C.G. vaccination and leukemia mortality. Lancet 2:638

    Google Scholar 

  • De Boer EC et al (1991) Presence of activated lymphocytes in the urine of patients with superficial bladder cancer after intravesical immunotherapy with bacillus Calmette-Guerin. Cancer Immunol Immunother 33:411–416

    Article  PubMed  Google Scholar 

  • de Boer EC et al (1997) Role of interleukin-8 in onset of the immune response in intravesical BCG therapy for superficial bladder cancer. Urol Res 25:31–34

    Article  PubMed  Google Scholar 

  • de Boer EC, Rooyakkers SJ, Schamhart DH, de Reijke TM, Kurth KH (2005) BCG dose reduction by decreasing the instillation frequency: effects on local Th1/Th2 cytokine responses in a mouse model. Eur Urol 48:333–338

    Article  PubMed  CAS  Google Scholar 

  • De Larco JE, Wuertz BR, Furcht LT (2004) The potential role of neutrophils in promoting the metastatic phenotype of tumors releasing interleukin-8. Clin Cancer Res 10:4895–4900

    Article  PubMed  Google Scholar 

  • Dyrskjot L et al (2012) Expression of MAGE-A3, NY-ESO-1, LAGE-1 and PRAME in urothelial carcinoma. Br J Cancer 107:116–122

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Farid SG et al (2010) Correlation between postoperative infective complications and long-term outcomes after hepatic resection for colorectal liver metastasis. Ann Surg 251:91–100

    Article  PubMed  Google Scholar 

  • Ferlay J et al (2007) Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 18:581–592

    Article  CAS  PubMed  Google Scholar 

  • Ferlay J et al (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49:1374–1403

    Article  CAS  PubMed  Google Scholar 

  • Galdiero MR et al (2013) Tumor associated macrophages and neutrophils in cancer. Immunobiology 218:1402–1410

    Article  CAS  PubMed  Google Scholar 

  • Gan C, Mostafid H, Khan MS, Lewis DJ (2013) BCG immunotherapy for bladder cancer–the effects of substrain differences. Nat Rev Urol 10:580–588

    Article  CAS  PubMed  Google Scholar 

  • Gandhi NM, Morales A, Lamm DL (2013) Bacillus Calmette-Guerin immunotherapy for genitourinary cancer. BJU Int 112:288–297

    Article  CAS  PubMed  Google Scholar 

  • Gutkin DW, Shurin MR (2014) Clinical evaluation of systemic and local immune responses in cancer: time for integration. Cancer Immunol Immunother 63:45–57

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Herr HW, Pinsky CM, Whitmore WF Jr, Oettgen HF, Melamed MR (1983) Effect of intravesical Bacillus Calmette-Guerin (BCG) on carcinoma in situ of the bladder. Cancer 51:1323–1326

    Article  CAS  PubMed  Google Scholar 

  • Hoffmann P, Roumeguere T, Schulman C, van Velthoven R (2006) Use of statins and outcome of BCG treatment for bladder cancer. N Engl J Med 355:2705–2707

    Article  CAS  PubMed  Google Scholar 

  • Hoption Cann SA, van Netten JP, van Netten C (2003) Dr William Coley and tumour regression: a place in history or in the future. Postgrad Med J 79:672–680

    CAS  PubMed Central  PubMed  Google Scholar 

  • Huh SJ, Liang S, Sharma A, Dong C, Robertson GP (2010) Transiently entrapped circulating tumor cells interact with neutrophils to facilitate lung metastasis development. Cancer Res 70:6071–6082

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ingersoll MA, Albert ML (2013) From infection to immunotherapy: host immune responses to bacteria at the bladder mucosa. Mucosal Immunol 6:1041–1053

    CAS  PubMed  Google Scholar 

  • Jackson AM 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. Clin Exp Immunol 99:369–375

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kaplan AL, Litwin MS, Chamie K (2014) The future of bladder cancer care in the USA. Nat Rev Urol 11:59–62

    Article  PubMed  Google Scholar 

  • Kavoussi LR, Brown EJ, Ritchey JK, Ratliff TL (1990) Fibronectin-mediated Calmette-Guerin bacillus attachment to murine bladder mucosa. Requirement for the expression of an antitumor response. J Clin Invest 85:62–67

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kelley DR et al (1985) Intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer: effect of bacillus Calmette-Guerin viability on treatment results. J Urol 134:48–53

    CAS  PubMed  Google Scholar 

  • Kemp TJ 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kolls JK, Linden A (2004) Interleukin-17 family members and inflammation. Immunity 21:467–476

    Article  CAS  PubMed  Google Scholar 

  • Kreider JW, Bartlett GL, Boyer CM, Purnell DM (1979) Conditions for effective Bacillus Calmette-Guerin immunotherapy of postsurgical metastases of 13762A rat mammary adenocarcinoma. Cancer Res 39:987–992

    CAS  PubMed  Google Scholar 

  • Lamm DL, Harris SC, Gittes RF (1977) Bacillus Calmette-Guerin and dinitrochlorobenzene immunotherapy of chemically induced bladder tumors. Investig Urol 14:369–372

    CAS  Google Scholar 

  • Lamm DL et al (1980) Bacillus Calmette-Guerin immunotherapy of superficial bladder cancer. J Urol 124:38–40

    CAS  PubMed  Google Scholar 

  • Lamm DL, Thor DE, Winters WD, Stogdill VD, Radwin HM (1981) BCG immunotherapy of bladder cancer: inhibition of tumor recurrence and associated immune responses. Cancer 48:82–88

    Article  CAS  PubMed  Google Scholar 

  • Lattime EC, Gomella LG, McCue PA (1992) Murine bladder carcinoma cells present antigen to BCG-specific CD4+ T-cells. Cancer Res 52:4286–4290

    CAS  PubMed  Google Scholar 

  • Lerner SP (2005) Bladder cancer clinical trials. Urol Oncol 23:275–279

    Article  PubMed  Google Scholar 

  • Lima L, Dinis-Ribeiro M, Longatto-Filho A, Santos L (2012) Predictive biomarkers of bacillus Calmette-Guerin immunotherapy response in bladder cancer: where are we now? Adv Urol 2012:232609

    Article  PubMed Central  PubMed  Google Scholar 

  • Lotan Y et al (2009) Key concerns about the current state of bladder cancer: a position paper from the Bladder Cancer Think Tank, the Bladder Cancer Advocacy Network, and the Society of Urologic Oncology. Cancer 115:4096–4103

    Article  PubMed  Google Scholar 

  • Luca S, Mihaescu T (2013) History of BCG vaccine. Maedica 8:53–58

    PubMed Central  PubMed  Google Scholar 

  • Ludwig AT et al (2004) Tumor necrosis factor-related apoptosis-inducing ligand: a novel mechanism for Bacillus Calmette-Guerin-induced antitumor activity. Cancer Res 64:3386–3390

    Article  CAS  PubMed  Google Scholar 

  • Luftenegger W et al (1996) Intravesical versus intravesical plus intradermal bacillus Calmette-Guerin: a prospective randomized study in patients with recurrent superficial bladder tumors. J Urol 155:483–487

    Article  CAS  PubMed  Google Scholar 

  • Mangtani P et al (2014) Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials. Clin Infect Dis 58:470–480

    Article  PubMed  Google Scholar 

  • Marits P et al (2006) Detection of immune responses against urinary bladder cancer in sentinel lymph nodes. Eur Urol 49:59–70

    Article  PubMed  Google Scholar 

  • Mathe G et al (1972) Attempts at stimulation of immune response in acute lymphoid leukaemia. Proc R Soc Med 65:266–270

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mavligit GM et al (1975) Adjuvant immunotherapy and chemoimmunotherapy in colorectal cancer of the Dukes’ C classification. Preliminary clinical results. Cancer 36:2421–2427

    Article  CAS  PubMed  Google Scholar 

  • McDonald B, Urrutia R, Yipp BG, Jenne CN, Kubes P (2012) Intravascular neutrophil extracellular traps capture bacteria from the bloodstream during sepsis. Cell Host Microbe 12:324–333

    Article  CAS  PubMed  Google Scholar 

  • McKhann CF, Gunnarsson A (1974) Approaches to immunotherapy. Cancer 34(suppl):1521–1531

    Article  PubMed  Google Scholar 

  • Morales A, Eidinger D, Bruce AW (1976) Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol 116:180–183

    CAS  PubMed  Google Scholar 

  • Noon AP, Kulkarni GS (2014) All bacillus Calmette-Guerin (BCG) strains are equal, but some BCG strains are more equal than others. Eur Urol 66(4):689–691. doi:10.1016/j.eururo.2014.04.008, Epub 2014 Apr 28

    Article  PubMed  Google Scholar 

  • Pan G et al (1997a) An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science 277:815–818

    Article  CAS  PubMed  Google Scholar 

  • Pan G et al (1997b) The receptor for the cytotoxic ligand TRAIL. Science 276:111–113

    Article  CAS  PubMed  Google Scholar 

  • Papayannopoulos V, Zychlinsky A (2009) NETs: a new strategy for using old weapons. Trends Immunol 30:513–521

    Article  CAS  PubMed  Google Scholar 

  • Pinsky CM et al (1985) Intravesical administration of bacillus Calmette-Guerin in patients with recurrent superficial carcinoma of the urinary bladder: report of a prospective, randomized trial. Cancer Treat Rep 69:47–53

    CAS  PubMed  Google Scholar 

  • Prescott S, James K, Hargreave TB, Chisholm GD, Smyth JF (1992) Intravesical Evans strain BCG therapy: quantitative immunohistochemical analysis of the immune response within the bladder wall. J Urol 147:1636–1642

    CAS  PubMed  Google Scholar 

  • Ratliff TL, Palmer JO, McGarr JA, Brown EJ (1987a) Intravesical Bacillus Calmette-Guerin therapy for murine bladder tumors: initiation of the response by fibronectin-mediated attachment of Bacillus Calmette-Guerin. Cancer Res 47:1762–1766

    CAS  PubMed  Google Scholar 

  • Ratliff TL, Gillen D, Catalona WJ (1987b) Requirement of a thymus dependent immune response for BCG-mediated antitumor activity. J Urol 137:155–158

    CAS  PubMed  Google Scholar 

  • Ratliff TL, Ritchey JK, Yuan JJ, Andriole GL, Catalona WJ (1993) T-cell subsets required for intravesical BCG immunotherapy for bladder cancer. J Urol 150:1018–1023

    CAS  PubMed  Google Scholar 

  • Redelman-Sidi G, Glickman MS, Bochner BH (2014) The mechanism of action of BCG therapy for bladder cancer–a current perspective. Nat Rev Urol 11:153–162

    Article  CAS  PubMed  Google Scholar 

  • Rentsch CA et al (2014) Bacillus Calmette-Guerin strain differences have an impact on clinical outcome in bladder cancer immunotherapy. Eur Urol 66(4):677–688. doi:10.1016/j.eururo.2014.02.061, Epub 2014 Mar 12

    Article  PubMed  Google Scholar 

  • Riemensberger J, Bohle A, Brandau S (2002) IFN-gamma and IL-12 but not IL-10 are required for local tumour surveillance in a syngeneic model of orthotopic bladder cancer. Clin Exp Immunol 127:20–26

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ritz N, Curtis N (2009) Mapping the global use of different BCG vaccine strains. Tuberculosis 89:248–251

    Article  PubMed  Google Scholar 

  • Rosenberg SA (1975) Future prospects for immunotherapy. Cancer 36:821–824

    Article  CAS  PubMed  Google Scholar 

  • Rosenthal SR et al (1972) BCG vaccination and leukemia mortality. JAMA 222:1543–1544

    Article  CAS  PubMed  Google Scholar 

  • Saint F et al (2001) T helper 1/2 lymphocyte urinary cytokine profiles in responding and nonresponding patients after 1 and 2 courses of bacillus Calmette-Guerin for superficial bladder cancer. J Urol 166:2142–2147

    Article  CAS  PubMed  Google Scholar 

  • Saint F et al (2002) Prognostic value of a T helper 1 urinary cytokine response after intravesical bacillus Calmette-Guerin treatment for superficial bladder cancer. J Urol 167:364–367

    Article  PubMed  Google Scholar 

  • Sarica K et al (1995) Evaluation of cellular immunity following bacillus Calmette-Guerin therapy in patients with superficial bladder cancer. Urol Int 54:137–141

    Article  CAS  PubMed  Google Scholar 

  • Sarosdy MF, Lamm DL (1989) Long-term results of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer. J Urol 142:719–722

    CAS  PubMed  Google Scholar 

  • Schmitz-Drager BJ et al (2014 Oct) Considerations on the use of urine markers in the management of patients with low-/intermediate-risk non-muscle invasive bladder cancer. Urol Oncol 32(7):1061–1068. doi:10.1016/j.urolonc.2013.10.010, Epub 2014 Jan 9

  • Schussler O et al (2006) Postoperative pneumonia after major lung resection. Am J Respir Crit Care Med 173:1161–1169

    Article  PubMed  Google Scholar 

  • Schwentner C, Stenzl A, Gakis G (2012) Monitoring high-risk bladder cancer. Curr Opin Urol 22:421–426

    Article  PubMed  Google Scholar 

  • Secanella-Fandos S, Luquin M, Julian E (2013) Connaught and Russian strains showed the highest direct antitumor effects of different Bacillus Calmette-Guerin substrains. J Urol 189:711–718

    Article  PubMed  Google Scholar 

  • Sengiku A et al (2013) A prospective comparative study of intravesical bacillus Calmette-Guerin therapy with the Tokyo or Connaught strain for nonmuscle invasive bladder cancer. J Urol 190:50–54

    Article  PubMed  Google Scholar 

  • Sharma P et al (2003) Frequency of NY-ESO-1 and LAGE-1 expression in bladder cancer and evidence of a new NY-ESO-1 T-cell epitope in a patient with bladder cancer. Cancer Immun 3:19

    Article  PubMed  Google Scholar 

  • Sheridan JP et al (1997) Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277:818–821

    Article  CAS  PubMed  Google Scholar 

  • Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63:11–30

    Article  PubMed  Google Scholar 

  • Sievert KD et al (2009) Economic aspects of bladder cancer: what are the benefits and costs? World J Urol 27:295–300

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Singer S et al (2013) Quality of life in patients with muscle invasive and non-muscle invasive bladder cancer. Support Care Cancer 21:1383–1393

    Article  CAS  PubMed  Google Scholar 

  • Suttmann H, Lehan N, Bohle A, Brandau S (2003) Stimulation of neutrophil granulocytes with Mycobacterium bovis bacillus Calmette-Guerin induces changes in phenotype and gene expression and inhibits spontaneous apoptosis. Infect Immun 71:4647–4656

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Suttmann H et al (2006) Neutrophil granulocytes are required for effective Bacillus Calmette-Guerin immunotherapy of bladder cancer and orchestrate local immune responses. Cancer Res 66:8250–8257

    Article  CAS  PubMed  Google Scholar 

  • Sylvester RJ, van der Meijden AP, Lamm DL (2002) Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol 168:1964–1970

    Article  CAS  PubMed  Google Scholar 

  • Sylvester RJ et al (2006) Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 49:466–465; discussion 475–467

    Article  PubMed  Google Scholar 

  • Takeuchi A et al (2011) IL-17 production by gammadelta T cells is important for the antitumor effect of Mycobacterium bovis bacillus Calmette-Guerin treatment against bladder cancer. Eur J Immunol 41:246–251

    Article  CAS  PubMed  Google Scholar 

  • Tan JK, Ho VC (1993) Pooled analysis of the efficacy of bacille Calmette-Guerin (BCG) immunotherapy in malignant melanoma. J Dermatol Surg Oncol 19:985–990

    Article  CAS  PubMed  Google Scholar 

  • Tecchio C et al (2004) IFNalpha-stimulated neutrophils and monocytes release a soluble form of TNF-related apoptosis-inducing ligand (TRAIL/Apo-2 ligand) displaying apoptotic activity on leukemic cells. Blood 103:3837–3844

    Article  CAS  PubMed  Google Scholar 

  • Thalmann GN, Dewald B, Baggiolini M, Studer UE (1997) Interleukin-8 expression in the urine after bacillus Calmette-Guerin therapy: a potential prognostic factor of tumor recurrence and progression. J Urol 158:1340–1344

    Article  CAS  PubMed  Google Scholar 

  • Thalmann GN et al (2000) Urinary Interleukin-8 and 18 predict the response of superficial bladder cancer to intravesical therapy with bacillus Calmette-Guerin. J Urol 164:2129–2133

    Article  CAS  PubMed  Google Scholar 

  • Torrado E, Robinson RT, Cooper AM (2011) Cellular response to mycobacteria: balancing protection and pathology. Trends Immunol 32:66–72

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Watanabe E et al (2003) Urinary interleukin-2 may predict clinical outcome of intravesical bacillus Calmette-Guerin immunotherapy for carcinoma in situ of the bladder. Cancer Immunol Immunother 52:481–486

    Article  CAS  PubMed  Google Scholar 

  • Wiley SR et al (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3:673–682

    Article  CAS  PubMed  Google Scholar 

  • Winters WD, Lamm DL (1981) Antibody responses to Bacillus Calmette-Guerin during immunotherapy in bladder cancer patients. Cancer Res 41:2672–2676

    CAS  PubMed  Google Scholar 

  • Wolfe SA, Tracey DE, Henney CS (1976) Introduction of “natural” killer’ cells by BCG. Nature 262:584–586

    Article  CAS  PubMed  Google Scholar 

  • Zbar B, Rapp HJ (1974) Immunotherapy of guinea pig cancer with BCG. Cancer 34(suppl):1532–1540

    Article  PubMed  Google Scholar 

  • Zbar B, Tanaka T (1971) Immunotherapy of cancer: regression of tumors after intralesional injection of living Mycobacterium bovis. Science 172:271–273

    Article  CAS  PubMed  Google Scholar 

  • Zhao W et al (2000) Role of a bacillus Calmette-Guerin fibronectin attachment protein in BCG-induced antitumor activity. Int J Cancer 86:83–88

    Article  CAS  PubMed  Google Scholar 

  • Zuiverloon TC et al (2012) Markers predicting response to bacillus Calmette-Guerin immunotherapy in high-risk bladder cancer patients: a systematic review. Eur Urol 61:128–145

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unité d’Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur, 25 Rue du Dr Roux, Batiment Metchnikoff, 75015, Paris, France

    Hana Zdimerova, Matthew L. Albert & Molly A. Ingersoll

  2. INSERM U818, Department of Immunology, Institut Pasteur, 25 Rue du Dr Roux, Batiment Metchnikoff, 75015, Paris, France

    Hana Zdimerova, Matthew L. Albert & Molly A. Ingersoll

Authors
  1. Hana Zdimerova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew L. Albert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Molly A. Ingersoll
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Molly A. Ingersoll .

Editor information

Editors and Affiliations

  1. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

    Michael R. Shurin

  2. Department of Immunology, Roswell Park Cancer Institute, Buffalo, New York, USA

    Yasmin Thanavala

  3. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA

    Nahed Ismail

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Zdimerova, H., Albert, M.L., Ingersoll, M.A. (2015). Harnessing the Host Immune Response to Infection – BCG Immunotherapy for Bladder Cancer. In: Shurin, M., Thanavala, Y., Ismail, N. (eds) Infection and Cancer: Bi-Directorial Interactions. Springer, Cham. https://doi.org/10.1007/978-3-319-20669-1_18

Download citation

Publish with us

Policies and ethics

Search

Navigation