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World Journal of Urology
Published in: World Journal of Urology 1/2016

01-01-2016 | Topic Paper

Immune checkpoint inhibitors: a new frontier in bladder cancer

Authors: Max Kates, Nikolai A. Sopko, Hotaka Matsui, Charles G. Drake, Noah M. Hahn, Trinity J. Bivalacqua

Published in: World Journal of Urology | Issue 1/2016

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Abstract

Immunotherapy is rapidly changing the field of urologic oncology. In this review, we discuss the role of the immune system in general and place a particular emphasis on the biology of the immune checkpoint and its role in cancer. Bladder cancer, as one of the most immunogenic neoplasms, is an exciting target for immune checkpoint inhibition. Early preclinical data and human trial experience suggest that this new drug class may shape bladder cancer therapy for years to come.
Literature
1.
Abdollah F, Gandaglia G, Thuret R, Schmitges J, Tian Z, Jeldres C, Passoni NM, Briganti A, Shariat SF, Perrotte P (2013) Incidence, survival and mortality rates of stage-specific bladder cancer in United States: a trend analysis. Cancer Epidemiol 37:219–225PubMedCrossRef
2.
3.
Brahmer JR, Tykodi SS, Chow LQ, Hwu W, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465PubMedPubMedCentralCrossRef
4.
Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Schuster SJ, Millenson MM, Cattry D, Freeman GJ (2015) PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med 372:311–319PubMedPubMedCentralCrossRef
5.
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454PubMedPubMedCentralCrossRef
6.
Hamid O, Robert C, Daud A, Hodi FS, Hwu W, Kefford R, Wolchok JD, Hersey P, Joseph RW, Weber JS (2013) Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 369:134–144PubMedPubMedCentralCrossRef
7.
Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723PubMedPubMedCentralCrossRef
8.
Robert C, Thomas L, Bondarenko I, O’Day S, Weber J, Garbe C, Lebbe C, Baurain J, Testori A, Grob J (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364:2517–2526PubMedCrossRef
9.
Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, Bellmunt J, Burris HA, Petrylak DP, Teng S (2014) MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 515:558–562PubMedCrossRef
10.
Fridman WH, Galon J, Pages F, Tartour E, Sautes-Fridman C, Kroemer G (2011) Prognostic and predictive impact of intra- and peritumoral immune infiltrates. Cancer Res 71:5601–5605PubMedCrossRef
11.
Pages F, Galon J, Dieu-Nosjean M, Tartour E, Sautes-Fridman C, Fridman W (2010) Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene 29:1093–1102PubMedCrossRef
12.
Zitvogel L, Kepp O, Kroemer G (2011) Immune parameters affecting the efficacy of chemotherapeutic regimens. Nat Rev Clin Oncol 8:151–160PubMedCrossRef
13.
Schreiber RD, Old LJ, Smyth MJ (2011) Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 331:1565–1570PubMedCrossRef
14.
Colombo MP, Piconese S (2007) Regulatory T-cell inhibition versus depletion: the right choice in cancer immunotherapy. Nat Rev Cancer 7:880–887PubMedCrossRef
15.
Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12:252–264PubMedCrossRef
16.
Schwartz RH (1992) Costimulation of T lymphocytes: the role of CD28, CTLA-4, and B7/BB1 in interleukin-2 production and immunotherapy. Cell 71:1065–1068PubMedCrossRef
17.
Azuma M, Ito D, Yagita H, Okumura K, Phillips JH, Lanier LL, Somoza C (1993) B70 antigen is a second ligand for CTLA-4 and CD28. Nature 366:76–79PubMedCrossRef
18.
Hathcock KS, Laszlo G, Dickler HB, Bradshaw J, Linsley P, Hodes RJ (1993) Identification of an alternative CTLA-4 ligand costimulatory for T cell activation. Science 262:905–907PubMedCrossRef
19.
Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T, Miyara M, Fehervari Z, Nomura T, Sakaguchi S (2008) CTLA-4 control over Foxp3+ regulatory T cell function. Science 322:271–275PubMedCrossRef
20.
Leach DR, Krummel MF, Allison JP (1996) Enhancement of antitumor immunity by CTLA-4 blockade. Science 271:1734–1736PubMedCrossRef
21.
O’Day SJ, Maio M, Chiarion-Sileni V, Gajewski TF, Pehamberger H, Bondarenko IN, Queirolo P, Lundgren L, Mikhailov S, Roman L, Verschraegen C, Humphrey R, Ibrahim R, de Pril V, Hoos A, Wolchok JD (2010) Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. Ann Oncol 21:1712–1717PubMedCrossRef
22.
23.
Gao J, He Q, Subudhi S, Aparicio A, Zurita-Saavedra A, Lee DH, Jimenez C, Suarez-Almazor M, Sharma P (2015) Review of immune-related adverse events in prostate cancer patients treated with ipilimumab: MD Anderson experience. Oncogene. doi:10.​1038/​onc.​2015.​5
24.
Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K (2002) Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 8:793–800PubMedCrossRef
25.
Rosenwald A, Wright G, Leroy K, Yu X, Gaulard P, Gascoyne RD, Chan WC, Zhao T, Haioun C, Greiner TC, Weisenburger DD, Lynch JC, Vose J, Armitage JO, Smeland EB, Kvaloy S, Holte H, Delabie J, Campo E, Montserrat E, Lopez-Guillermo A, Ott G, Muller-Hermelink HK, Connors JM, Braziel R, Grogan TM, Fisher RI, Miller TP, LeBlanc M, Chiorazzi M, Zhao H, Yang L, Powell J, Wilson WH, Jaffe ES, Simon R, Klausner RD, Staudt LM (2003) Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med 198:851–862PubMedPubMedCentralCrossRef
26.
Kim J, Myers AC, Chen L, Pardoll DM, Truong-Tran Q, Lane AP, McDyer JF, Fortuno L, Schleimer RP (2005) Constitutive and inducible expression of b7 family of ligands by human airway epithelial cells. Am J Respir Cell Mol Biol 33:280–289PubMedPubMedCentralCrossRef
27.
Francisco LM, Salinas VH, Brown KE, Vanguri VK, Freeman GJ, Kuchroo VK, Sharpe AH (2009) PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med 206:3015–3029PubMedPubMedCentralCrossRef
28.
Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS (2014) Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 32:1020–1030PubMedCrossRef
29.
30.
Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA (2013) Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499:214–218PubMedPubMedCentralCrossRef
31.
Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, Miller ML, Rekhtman N, Moreira AL, Ibrahim F, Bruggeman C, Gasmi B, Zappasodi R, Maeda Y, Sander C, Garon EB, Merghoub T, Wolchok JD, Schumacher TN, Chan TA (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:124–128PubMedCrossRef
32.
Sharma P, Shen Y, Wen S, Yamada S, Jungbluth AA, Gnjatic S, Bajorin DF, Reuter VE, Herr H, Old LJ, Sato E (2007) CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc Natl Acad Sci USA 104:3967–3972PubMedPubMedCentralCrossRef
33.
Nakanishi J, Wada Y, Matsumoto K, Azuma M, Kikuchi K, Ueda S (2007) Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers. Cancer Immunol Immunother 56:1173–1182PubMedCrossRef
34.
Boorjian SA, Sheinin Y, Crispen PL, Farmer SA, Lohse CM, Kuntz SM, Leibovich BC, Kwon ED, Frank I (2008) T-cell coregulatory molecule expression in urothelial cell carcinoma: clinicopathologic correlations and association with survival. Clin Cancer Res 14:4800–4808PubMedCrossRef
35.
Xylinas E, Robinson B, Kluth L, Volkmer B, Hautmann R, Küfer R, Zerbib M, Kwon E, Thompson R, Boorjian S (2014) Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder. Eur J Surg Oncol (EJSO) 40:121–127CrossRef
36.
Bellmunt J, Mullane SA, Werner L, Fay AP, Callea M, Leow JJ, Taplin ME, Choueiri TK, Hodi FS, Freeman GJ, Signoretti S (2015) Association of PD-L1 expression on tumor-infiltrating mononuclear cells and overall survival in patients with urothelial carcinoma. Ann Oncol 26:812–817PubMedCrossRef
37.
Redelman-Sidi G, Glickman MS, Bochner BH (2014) The mechanism of action of BCG therapy for bladder cancer—a current perspective. Nat Rev Urol 11:153–162PubMedCrossRef
38.
Morales A, Eidinger D, Bruce AW (1976) Intracavitary bacillus Calmette–Guerin in the treatment of superficial bladder tumors. J Urol 116:180–183PubMed
39.
Brausi M, Witjes JA, Lamm D, Persad R, Palou J, Colombel M, Buckley R, Soloway M, Akaza H, Böhle A (2011) A review of current guidelines and best practice recommendations for the management of nonmuscle invasive bladder cancer by the International Bladder Cancer Group. J Urol 186:2158–2167PubMedCrossRef
40.
Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Böhle A, Palou-Redorta J, Rouprêt M (2011) EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. Eur Urol 59:997–1008PubMedCrossRef
41.
O’Donnell MA, Luo Y, Chen X, Szilvasi A, Hunter SE, Clinton SK (1999) Role of IL-12 in the induction and potentiation of IFN-gamma in response to bacillus Calmette–Guerin. J Immunol 163:4246–4252PubMed
42.
De Boer E, De Jong W, Steerenberg P, Aarden L, Tetteroo E, De Groot E, Van der Meijden A, Vegt P, Debruyne F, Ruitenberg E (1992) Induction of urinary interleukin-1 (IL-1), IL-2, IL-6, and tumour necrosis factor during intravesical immunotherapy with bacillus Calmette–Guerin in superficial bladder cancer. Cancer Immunol Immunother 34:306–312PubMedCrossRef
43.
Bohle A, Gerdes J, Ulmer AJ, Hofstetter AG, Flad HD (1990) Effects of local bacillus Calmette–Guerin therapy in patients with bladder carcinoma on immunocompetent cells of the bladder wall. J Urol 144:53–58PubMed
44.
Kamat AM, Briggman J, Urbauer DL, Svatek R, Nogueras Gonzalez GM, Anderson R, Grossman HB, Prat F, Dinney CP (2015) Cytokine panel for response to intravesical therapy (CyPRIT): nomogram of changes in urinary cytokine levels predicts patient response to bacillus Calmette–Guerin. Eur Urol. doi:10.​1016/​jeururo.​2015.​06.​023
45.
Bisiaux A, Thiounn N, Timsit MO, Eladaoui A, Chang HH, Mapes J, Mogenet A, Bresson JL, Prie D, Bechet S, Baron C, Sadorge C, Thomas S, Albert EB, Albert PS, Albert ML (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 181:1571–1580PubMedCrossRef
46.
Biot C, Rentsch CA, Gsponer JR, Birkhauser FD, Jusforgues-Saklani H, Lemaitre F, Auriau C, Bachmann A, Bousso P, Demangel C, Peduto L, Thalmann GN, Albert ML (2012) Preexisting BCG-specific T cells improve intravesical immunotherapy for bladder cancer. Sci Transl Med 4:137ra72PubMedCrossRef
47.
Sonoda T, Sugimura K, Ikemoto S, Kawashima H, Nakatani T (2007) Significance of target cell infection and natural killer cells in the anti-tumor effects of bacillus Calmette–Guerin in murine bladder cancer. Oncol Rep 17:1469–1474PubMed
48.
Luo Y, Yamada H, Evanoff DP, Chen X (2006) Role of Th1-stimulating cytokines in bacillus Calmette–Guerin (BCG)-induced macrophage cytotoxicity against mouse bladder cancer MBT-2 cells. Clin Exp Immunol 146:181–188PubMedPubMedCentralCrossRef
49.
Suttmann H, Riemensberger J, Bentien G, Schmaltz D, Stockle M, Jocham D, Bohle A, Brandau S (2006) Neutrophil granulocytes are required for effective bacillus Calmette–Guerin immunotherapy of bladder cancer and orchestrate local immune responses. Cancer Res 66:8250–8257PubMedCrossRef
50.
Inman BA, Sebo TJ, Frigola X, Dong H, Bergstralh EJ, Frank I, Fradet Y, Lacombe L, Kwon ED (2007) PD-L1 (B7-H1) expression by urothelial carcinoma of the bladder and BCG-induced granulomata: associations with localized stage progression. Cancer 109:1499–1505PubMedCrossRef
51.
Hurwitz MA, Yao X, Hafez N, Schalper K, Rimm D, Petrylak D (2015) The effect of BCG intravesical therapy and recurrence on PDL1 expression in non-invasive bladder cancers. J Clin Oncol 33:e15504CrossRef
52.
Carthon BC, Wolchok JD, Yuan J, Kamat A, Ng Tang DS, Sun J, Ku G, Troncoso P, Logothetis CJ, Allison JP, Sharma P (2010) Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial. Clin Cancer Res 16:2861–2871PubMedPubMedCentralCrossRef
53.
Kim JW, Bellmunt J, Powles T, Loriot Y, Vogelzang NJ, Zambrano CC, Burris HA, Teng SM, Shen X, Bruey J (2015) Clinical activity, safety, and biomarkers of MPDL3280A in metastatic urothelial bladder cancer: additional analysis from phase IA study. J Clin Oncol (Meeting Abstracts) 33(7)
54.
Petrylak DP, Powles T, Bellmunt J, Braiteh FS, Loriot Y, Cruz Zambrano C, Burris HA, Kim JW, Teng SM, Bruey J (2015) A phase Ia study of MPDL3280A (anti-PDL1): updated response and survival data in urothelial bladder cancer (UBC). J Clin Oncol (Meeting Abstracts) 33
55.
O’Donnell PH, Plimack ER, Bellmunt J, Berger R, Montgomery RB, Heath K, Dolled-Filhart M, Pathiraja K, Gause CK, Cheng JD (2015) Pembrolizumab (Pembro; MK-3475) for advanced urothelial cancer: results of a phase IB study. J Clin Oncol (Meeting Abstracts) 33(7)
56.
Ngiow SF, von Scheidt B, Akiba H, Yagita H, Teng MW, Smyth MJ (2011) Anti-TIM3 antibody promotes T cell IFN-gamma-mediated antitumor immunity and suppresses established tumors. Cancer Res 71:3540–3551PubMedCrossRef
57.
Jing W, Gershan JA, Weber J, Tlomak D, McOlash L, Sabatos-Peyton C, Johnson BD (2015) Combined immune checkpoint protein blockade and low dose whole body irradiation as immunotherapy for myeloma. J Immunother Cancer 3:2-014-0043-z. eCollection 2015
58.
Topalian SL, Drake CG, Pardoll DM (2015) Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 27:450–461PubMedCrossRef
59.
Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372:2509–2520PubMedCrossRef
60.
Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V (2014) PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 515:568–571PubMedPubMedCentralCrossRef
61.
Herbst RS, Soria J, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN (2014) Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515:563–567PubMedCrossRef
62.
Liu J, Baras AS, Gandhi NM, Guner G, Munari E, Faraj S, Taube JM, Schoenberg M, Hahn NM, Drake CG (2015) PDL1 status in muscle-invasive urothelial carcinoma in the context of neoadjuvant cisplatin-based chemotherapy. J Clin Oncol (Meeting Abstracts) 33(7)
63.
Wei S, Egenti MU, Teitz-Tennenbaum S, Zou W, Chang AE (2013) Effects of tumor irradiation on host T-regulatory cells and systemic immunity in the context of adoptive T-cell therapy in mice. J Immunother 36:124–132PubMedPubMedCentralCrossRef
64.
Sharabi AB, Nirschl CJ, Kochel CM, Nirschl TR, Francica BJ, Velarde E, Deweese TL, Drake CG (2015) Stereotactic radiation therapy augments antigen-specific pd-1-mediated antitumor immune responses via cross-presentation of tumor antigen. Cancer Immunol Res 3:345–355PubMedCrossRef
65.
66.
Crittenden M, Kohrt H, Levy R, Jones J, Camphausen K, Dicker A, Demaria S, Formenti S (2015) Current clinical trials testing combinations of immunotherapy and radiation. Semin Radiat Oncol 25:54–64PubMedPubMedCentralCrossRef
67.
Ngiow SF, McArthur GA, Smyth MJ (2015) Radiotherapy complements immune checkpoint blockade. Cancer Cell 27:437–438PubMedCrossRef
68.
Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM (2015) Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 520:373–377. doi:10.​1038/​nature14292 PubMedCrossRef
Metadata
Title
Immune checkpoint inhibitors: a new frontier in bladder cancer
Authors
Max Kates
Nikolai A. Sopko
Hotaka Matsui
Charles G. Drake
Noah M. Hahn
Trinity J. Bivalacqua
Publication date
01-01-2016
Publisher
Springer Berlin Heidelberg
Published in
World Journal of Urology / Issue 1/2016
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-015-1709-y

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