{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T22:11:43Z","timestamp":1785276703768,"version":"3.55.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T00:00:00Z","timestamp":1659916800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T00:00:00Z","timestamp":1659916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100007392","name":"Instituto Nacional de Ci\u00eancia e Tecnologia em Nanomateriais de Carbono","doi-asserted-by":"publisher","award":["304747\/2018-1"],"award-info":[{"award-number":["304747\/2018-1"]}],"id":[{"id":"10.13039\/501100007392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Int Urol Nephrol"],"DOI":"10.1007\/s11255-022-03336-9","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T10:02:40Z","timestamp":1659952960000},"page":"2845-2853","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Castration immunoregulates toll-like receptor-4 in male bladder cancer"],"prefix":"10.1007","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2092-414X","authenticated-orcid":false,"given":"Leonardo Oliveira","family":"Reis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Clara Ciglioni","family":"Salustiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego Moreira","family":"Capibaribe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isis Gallani Avansini","family":"Kiehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernandes","family":"Denardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,8,8]]},"reference":[{"key":"3336_CR1","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1159\/000449256","volume":"97","author":"F Burge","year":"2016","unstructured":"Burge F, Kockelbergh R (2016) Closing the gender gap: can we improve bladder cancer survival in women? a systematic review of diagnosis, treatment, and outcomes. Urol Int 97:373\u2013379","journal-title":"Urol Int"},{"key":"3336_CR2","doi-asserted-by":"publisher","first-page":"234","DOI":"10.5114\/pjp.2018.79543","volume":"69","author":"S Elzamy","year":"2018","unstructured":"Elzamy S, Ms AA, Kandeel W (2018) The prognostic significance of androgen receptor and beta-catenin immunohistochemical expression in urothelial carcinoma with and without detrusor muscle invasion from an Egyptian institution. Pol J Pathol 69:234\u2013242","journal-title":"Pol J Pathol"},{"key":"3336_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2012\/181987","volume":"2012","author":"EJ Askeland","year":"2012","unstructured":"Askeland EJ, Newton MR, O\u2019Donnell MA, Luo Y (2012) Bladder cancer immunotherapy: BCG and beyond. Adv Urol 2012:1\u201313","journal-title":"Adv Urol"},{"issue":"4","key":"3336_CR4","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1038\/sj.bjc.6602026","volume":"91","author":"RF Bevers","year":"2004","unstructured":"Bevers RF, Kurth KH, Schamhart DH (2004) Role of urothelial cells in BCG immunotherapy for superficial bladder cancer. Br J Cancer 91(4):607\u2013612","journal-title":"Br J Cancer"},{"key":"3336_CR5","doi-asserted-by":"crossref","first-page":"656","DOI":"10.4049\/jimmunol.132.2.656","volume":"132","author":"Y Weinstein","year":"1984","unstructured":"Weinstein Y, Ran S, Segal S (1984) Sex-associated differences in the regulation of immune responses controlled by the MHC of the mouse. J Immunol 132:656\u2013661","journal-title":"J Immunol"},{"issue":"1","key":"3336_CR6","doi-asserted-by":"publisher","first-page":"1000267","DOI":"10.1371\/journal.ppat.1000267","volume":"5","author":"M Zuk","year":"2009","unstructured":"Zuk M (2009) The sicker sex. PLoS Pathog 5(1):1000267","journal-title":"PLoS Pathog"},{"issue":"8","key":"3336_CR7","doi-asserted-by":"publisher","first-page":"3255","DOI":"10.1182\/blood-2008-04-153627","volume":"112","author":"KM Williams","year":"2008","unstructured":"Williams KM, Lucas PJ, Bare CV, Wang J, Chu YW, Tayler E, Kapoor V, Gress RE (2008) CCL25 increases thymopoiesis after androgen withdrawal. Blood 112(8):3255\u20133263","journal-title":"Blood"},{"key":"3336_CR8","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1097\/ACM.0000000000002027","volume":"93","author":"SE Geller","year":"2018","unstructured":"Geller SE, Koch AR, Roesch P, Filut A, Hallgren E, Carnes M (2018) The more things change, the more they stay the same: a study to evaluate compliance with inclusion and assessment of women and minorities in randomized controlled trials. Acad Med 93:630\u2013635","journal-title":"Acad Med"},{"issue":"3","key":"3336_CR9","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1159\/000474484","volume":"31","author":"S Imada","year":"1997","unstructured":"Imada S, Akaza H, Ami Y, Koiso K, Ideyama Y, Takenaka T (1997) Promoting effects and mechanisms of action of androgen in bladder carcinogenesis in male rats. Eur Urol 31(3):360\u2013364","journal-title":"Eur Urol"},{"issue":"9","key":"3336_CR10","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1158\/1535-7163.MCT-20-0050","volume":"19","author":"T Mizushima","year":"2020","unstructured":"Mizushima T, Jiang G, Kawahara T, Li P, Han B, Inoue S, Kato HII, Jalalizadeh M, Miyagi E, Fukuda M, Reis LO, Miyamoto H (2020) Androgen receptor signaling reduces the efficacy of bacillus calmette-gu\u00e9rin therapy for bladder cancer via modulating rab27b-induced exocytosis. Mol Cancer Ther 19(9):1930\u20131942","journal-title":"Mol Cancer Ther"},{"issue":"31","key":"3336_CR11","doi-asserted-by":"publisher","first-page":"49169","DOI":"10.18632\/oncotarget.9994","volume":"7","author":"E Kashiwagi","year":"2016","unstructured":"Kashiwagi E, Ide H, Inoue S, Kawahara T, Zheng Y, Reis LO, Baras AS, Miyamoto H (2016) Androgen receptor activity modulates responses to cisplatin treatment in bladder cancer. Oncotarget 7(31):49169\u201349179","journal-title":"Oncotarget"},{"issue":"9","key":"3336_CR12","first-page":"980","volume":"14","author":"ACC Salustiano","year":"2021","unstructured":"Salustiano ACC, Riccetto E, Kiehl IG, Ossick MV, Ferrari KL, Denardi F, Reis LO (2021) Autochthonous male urothelial carcinoma immune competent model: from induction to BCG transurethral treatment. Int J Clin Exp Pathol 14(9):980\u2013986","journal-title":"Int J Clin Exp Pathol"},{"issue":"2","key":"3336_CR13","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1016\/j.juro.2011.10.022","volume":"187","author":"LO Reis","year":"2012","unstructured":"Reis LO, Ferreira U, Billis A, Cagnon VH, F\u00e1varo WJ (2012) Anti-angiogenic effects of the superantigen staphylococcal enterotoxin B and bacillus Calmette-Gu\u00e9rin immunotherapy for nonmuscle invasive bladder cancer. J Urol 187(2):438\u2013445","journal-title":"J Urol"},{"issue":"2","key":"3336_CR14","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1177\/106689690501300203","volume":"13","author":"R Montironi","year":"2005","unstructured":"Montironi R, Lopez-Beltran A (2005) The 2004 WHO classification of bladder tumors: a summary and commentary. Int J Surg Pathol 13(2):143\u2013153","journal-title":"Int J Surg Pathol"},{"key":"3336_CR15","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1590\/S0102-86502011000800019","volume":"2","author":"LO Reis","year":"2011","unstructured":"Reis LO, Sopena JM, F\u00e1varo WJ, Martin MC, Sim\u00e3o AF, Reis RB, Andrade MF, Domenech JD, Cardo CC (2011) Anatomical features of the urethra and urinary bladder catheterization in female mice and rats. an essential translational tool. Acta Cir Bras 2:106\u2013110","journal-title":"Acta Cir Bras"},{"key":"3336_CR16","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/ni1059","volume":"5","author":"Y Yang","year":"2004","unstructured":"Yang Y, Huang CT, Huang X (2004) Pardoll DM (2004) Persistent Toll-like receptor signals are required for reversal of regulatory T cell-mediated CD8 tolerance. Nat Immunol 5:508\u2013515","journal-title":"Nat Immunol"},{"key":"3336_CR17","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/s41577-019-0210-z","volume":"20","author":"SK Wculek","year":"2020","unstructured":"Wculek SK, Cueto FJ, Mujal AM, Melero I, Krummel MF, Sancho D (2020) Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol 20:7\u201324","journal-title":"Nat Rev Immunol"},{"key":"3336_CR18","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.3389\/fimmu.2018.01650","volume":"9","author":"A Vidyarthi","year":"2018","unstructured":"Vidyarthi A, Khan N, Agnihotri T, Negi S, Das DK, Aqdas M, Chatterjee D, Colegio OR, Tewari MK, Agrewala JN (2018) TLR-3 stimulation skews M2 macrophages to M1 through IFN-alphabeta signaling and restricts tumor progression. Front Immunol 9:1650","journal-title":"Front Immunol"},{"issue":"3","key":"3336_CR19","doi-asserted-by":"publisher","first-page":"e587","DOI":"10.1016\/j.clgc.2017.10.019","volume":"16","author":"JA Camargo","year":"2018","unstructured":"Camargo JA, Passos GR, Ferrari KL, Billis A, Saad MJA, Reis LO (2018) Intravesical immunomodulatory imiquimod enhances bacillus calmette-gu\u00e9rin downregulation of nonmuscle-invasive bladder cancer. Clin Genitourin Cancer 16(3):e587\u2013e593","journal-title":"Clin Genitourin Cancer"},{"issue":"3","key":"3336_CR20","doi-asserted-by":"publisher","first-page":"e003939","DOI":"10.1136\/jitc-2021-003939","volume":"10","author":"Y Zhang","year":"2022","unstructured":"Zhang Y, Huo F, Cao Q, Jia R, Huang Q, Wang ZA, Theodorescu D, Lv Q, Li P, Yan C (2022) FimH confers mannose-targeting ability to Bacillus Calmette-Guerin for improved immunotherapy in bladder cancer. J Immunother Cancer 10(3):e003939","journal-title":"J Immunother Cancer"},{"key":"3336_CR21","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1146\/annurev-cellbio-100616-060718","volume":"33","author":"KL Flanagan","year":"2017","unstructured":"Flanagan KL, Fink AL, Plebanski M, Klein SL (2017) Sex and gender differences in the outcomes of vaccination over the life course. Annu Rev Cell Dev Biol 33:577\u2013599","journal-title":"Annu Rev Cell Dev Biol"},{"issue":"2","key":"3336_CR22","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1073\/pnas.1321060111","volume":"111","author":"D Furman","year":"2014","unstructured":"Furman D, Hejblum BP, Simon N, Jojic V, Dekker CL, Thiebaut R, Tibshirani RJ, Davis MM (2014) Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination. Proc Natl Acad Sci USA 111(2):869\u2013874","journal-title":"Proc Natl Acad Sci USA"},{"issue":"3","key":"3336_CR23","doi-asserted-by":"publisher","first-page":"110.e19","DOI":"10.1016\/j.urolonc.2014.09.016","volume":"33","author":"PJ Olbert","year":"2015","unstructured":"Olbert PJ, Kesch C, Henrici M, Subtil FS, Honacker A, Hegele A, Hofmann R, H\u00e4nze J (2015) TLR4- and TLR9-dependent effects on cytokines, cell viability, and invasion in human bladder cancer cells. Urol Oncol 33(3):110.e19\u201327","journal-title":"Urol Oncol"},{"issue":"5","key":"3336_CR24","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1095\/biolreprod.106.053967","volume":"75","author":"AA Quintar","year":"2006","unstructured":"Quintar AA, Roth FD, De Paul AL, Aoki A, Maldonado CA (2006) Toll-like receptor 4 in rat prostate: modulation by testosterone and acute bacterial infection in epithelial and stromal cells. Biol Reprod 75(5):664\u2013672","journal-title":"Biol Reprod"},{"issue":"3","key":"3336_CR25","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1095\/biolreprod.107.063545","volume":"78","author":"JA Rettew","year":"2008","unstructured":"Rettew JA, Huet-Hudson YM, Marriott I (2008) Testosterone reduces macrophage expression in the mouse of toll-like receptor 4, a trigger for inflammation and innate immunity. Biol Reprod 78(3):432\u2013437","journal-title":"Biol Reprod"},{"issue":"2","key":"3336_CR26","doi-asserted-by":"publisher","first-page":"703","DOI":"10.21873\/anticanres.13166","volume":"39","author":"Y Kusuhara","year":"2019","unstructured":"Kusuhara Y, Daizumoto K, Kawai K, Hirayama K, Kowada M, Shintani T, Fukuhara Y, Dondoo T-O, Ozaki K, Tsuda M, Fukawa T, Nakatsuji H, Bando Y, Uehara H, Fukumori T, Takahashi M, Kanayama HO (2019) Low expression of toll-like receptor 4 is associated with poor prognosis in bladder cancer. Anticancer Res 39(2):703\u2013711","journal-title":"Anticancer Res"},{"issue":"3","key":"3336_CR27","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s00345-014-1329-y","volume":"33","author":"LO Reis","year":"2015","unstructured":"Reis LO, Ferrari K, Zamuner M, Rocha GZ, Billis A, F\u00e1varo WJ (2015) Urothelial carcinogen resistance driven by stronger Toll-like receptor 2 (TLR2) and Uroplakin III (UP III) defense mechanisms: a new model. World J Urol 33(3):413\u2013419","journal-title":"World J Urol"},{"issue":"7","key":"3336_CR28","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/nri3247","volume":"12","author":"CJ Desmet","year":"2012","unstructured":"Desmet CJ, Ishii KJ (2012) Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination. Nat Rev Immunol 12(7):479\u2013491","journal-title":"Nat Rev Immunol"},{"issue":"18","key":"3336_CR29","doi-asserted-by":"publisher","first-page":"e93397","DOI":"10.1172\/jci.insight.93397","volume":"2","author":"F Sato-Kaneko","year":"2017","unstructured":"Sato-Kaneko F, Yao S, Ahmadi A, Zhang SS, Hosoya T, Kaneda MM, Varner JA, Pu M, Messer KS, Guiducci C, Coffman RL, Kitaura K, Matsutani T, Suzuki R, Carson DA, Hayashi T, Cohen EE (2017) Combination immunotherapy with TLR agonists and checkpoint inhibitors suppresses head and neck cancer. JCI Insight 2(18):e93397","journal-title":"JCI Insight"},{"issue":"46","key":"3336_CR30","doi-asserted-by":"publisher","first-page":"E7240","DOI":"10.1073\/pnas.1608555113","volume":"113","author":"S Wang","year":"2016","unstructured":"Wang S, Campos J, Gallotta M, Gong M, Crain C, Naik E, Coffman RL, Guiducci C (2016) Intratumoral injection of a CpG oligonucleotide reverts resistance to PD-1 blockade by expanding multifunctional CD8+ T cells. Proc Natl Acad Sci USA 113(46):E7240\u2013E7249","journal-title":"Proc Natl Acad Sci USA"},{"issue":"5","key":"3336_CR31","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1016\/j.juro.2010.12.097","volume":"185","author":"C Ayari","year":"2011","unstructured":"Ayari C, Bergeron A, LaRue H, M\u00e9nard C, Fradet Y (2011) Toll-like receptors in normal and malignant human bladders. J Urol 185(5):1915\u20131921","journal-title":"J Urol"},{"issue":"6","key":"3336_CR32","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1089\/jwh.2019.8247","volume":"29","author":"ME Arnegard","year":"2020","unstructured":"Arnegard ME, Whitten LA, Hunter C, Clayton JA (2020) Sex as a biological variable: a 5-year progress report and call to action. J Womens Health (Larchmt) 29(6):858\u2013864","journal-title":"J Womens Health (Larchmt)"}],"container-title":["International Urology and Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11255-022-03336-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11255-022-03336-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11255-022-03336-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T23:25:14Z","timestamp":1676330714000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11255-022-03336-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,8]]},"references-count":32,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["3336"],"URL":"https:\/\/doi.org\/10.1007\/s11255-022-03336-9","relation":{},"ISSN":["1573-2584"],"issn-type":[{"value":"1573-2584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,8]]},"assertion":[{"value":"7 April 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"None.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"Local Animal Research Ethics Committee Approval no 4541\u20131\/2017 (CEUA\/UNICAMP).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants and\/or animals"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}