Abstract
The carcinogenesis of prostate cancer (PCa) results from a complex series of events. Chronic inflammation and infections are crucial in this context. Infiltrating M2 type macrophages, as well as neutrophils and T lymphocytes, contribute to PCa development, progression and response to therapy. The preliminary findings on the efficacy of immunotherapy in patients with PCa were not encouraging. However, a series of studies investigating anti-PD-L1 agents such as Atezolizumab, Avelumab and Durvalumab used alone or in combination with other immunotherapies, chemotherapy or locoregional approaches are in course in this tumor. In this review, we illustrate the role of immune cells and PD-L1 expression during PCa carcinogenesis and progression, with a focus on ongoing clinical trials on anti-PD-L1 agents in this context.
Keywords: Atezolizumab, avelumab, durvalumab, immunotherapy, PD-L1, prostate cancer.
Graphical Abstract
[1]
Drake CG, Lipson EJ, Brahmer JR. Breathing new life into immunotherapy: review of melanoma, lung and kidney cancer. Nat Rev Clin Oncol 2014; 11(1): 24-37.
[http://dx.doi.org/10.1038/nrclinonc.2013.208] [PMID: 24247168]
[http://dx.doi.org/10.1038/nrclinonc.2013.208] [PMID: 24247168]
[2]
Martin-Liberal J, Ochoa de Olza M, Hierro C, Gros A, Rodon J, Tabernero J. The expanding role of immunotherapy. Cancer Treat Rev 2017; 54: 74-86.
[http://dx.doi.org/10.1016/j.ctrv.2017.01.008] [PMID: 28231560]
[http://dx.doi.org/10.1016/j.ctrv.2017.01.008] [PMID: 28231560]
[3]
Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012; 366(26): 2443-54.
[http://dx.doi.org/10.1056/NEJMoa1200690] [PMID: 22658127]
[http://dx.doi.org/10.1056/NEJMoa1200690] [PMID: 22658127]
[4]
Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012; 366(26): 2455-65.
[http://dx.doi.org/10.1056/NEJMoa1200694] [PMID: 22658128]
[http://dx.doi.org/10.1056/NEJMoa1200694] [PMID: 22658128]
[5]
Lindberg J, Kristiansen A, Wiklund P, Grönberg H, Egevad L. Tracking the origin of metastatic prostate cancer. Eur Urol 2015; 67(5): 819-22.
[http://dx.doi.org/10.1016/j.eururo.2014.09.006] [PMID: 25246081]
[http://dx.doi.org/10.1016/j.eururo.2014.09.006] [PMID: 25246081]
[6]
Piva F, Santoni M, Scarpelli M, Briganti A, Montorsi F, Montironi R. Re: Johan Lindberg, Anna Kristiansen, Peter Wiklund, Henrik Grönberg, Lars Egevad. Tracking the origin of metastatic prostate Cancer. Eur Urol 2015; 68(6): e134-5.
[http://dx.doi.org/10.1016/j.eururo.2015.07.011] [PMID: 26215609]
[http://dx.doi.org/10.1016/j.eururo.2015.07.011] [PMID: 26215609]
[7]
Santoni M, Piva F, Scarpelli M, et al. The origin of prostate metastases: emerging insights. Cancer Metastasis Rev 2015; 34(4): 765-73.
[http://dx.doi.org/10.1007/s10555-015-9597-6] [PMID: 26363603]
[http://dx.doi.org/10.1007/s10555-015-9597-6] [PMID: 26363603]
[8]
Baca SC, Prandi D, Lawrence MS, et al. Punctuated evolution of prostate cancer genomes. Cell 2013; 153(3): 666-77.
[http://dx.doi.org/10.1016/j.cell.2013.03.021] [PMID: 23622249]
[http://dx.doi.org/10.1016/j.cell.2013.03.021] [PMID: 23622249]
[9]
Gundem G, Van Loo P, Kremeyer B, et al. ICGC Prostate Group The evolutionary history of lethal metastatic prostate cancer. Nature 2015; 520(7547): 353-7.
[http://dx.doi.org/10.1038/nature14347] [PMID: 25830880]
[http://dx.doi.org/10.1038/nature14347] [PMID: 25830880]
[10]
Ciccarese C, Santoni M, Massari F, et al. Metabolic alterations in renal and prostate cancer. Curr Drug Metab 2016; 17(2): 150-5.
[http://dx.doi.org/10.2174/1389200216666151015112356] [PMID: 26467063]
[http://dx.doi.org/10.2174/1389200216666151015112356] [PMID: 26467063]
[11]
Swinnen JV, Vanderhoydonc F, Elgamal AA, et al. Selective activation of the fatty acid synthesis pathway in human prostate cancer. Int J Cancer 2000; 88(2): 176-9.
[http://dx.doi.org/10.1002/1097-0215(20001015)88:2<176:AID-IJC5>3.0.CO;2-3] [PMID: 11004665]
[http://dx.doi.org/10.1002/1097-0215(20001015)88:2<176:AID-IJC5>3.0.CO;2-3] [PMID: 11004665]
[12]
Santoni M, Conti A, Burattini L, et al. Neuroendocrine differentiation in prostate cancer: novel morphological insights and future therapeutic perspectives. Biochim Biophys Acta 2014; 1846(2): 630-7.
[PMID: 25450825]
[PMID: 25450825]
[13]
Vitkin N, Nersesian S, Siemens DR, Koti M. The Tumor Immune Contexture of Prostate Cancer. Front Immunol 2019; 10: 603.
[http://dx.doi.org/10.3389/fimmu.2019.00603] [PMID: 30984182]
[http://dx.doi.org/10.3389/fimmu.2019.00603] [PMID: 30984182]
[14]
Sfanos KS, Hempel HA, De Marzo AM. The role of inflammation in prostate cancer. Adv Exp Med Biol 2014; 816: 153-81.
[http://dx.doi.org/10.1007/978-3-0348-0837-8_7] [PMID: 24818723]
[http://dx.doi.org/10.1007/978-3-0348-0837-8_7] [PMID: 24818723]
[15]
Gucalp A, Iyengar NM, Zhou XK, et al. Periprostatic adipose inflammation is associated with high-grade prostate cancer. Prostate Cancer Prostatic Dis 2017; 20(4): 418-23.
[http://dx.doi.org/10.1038/pcan.2017.31] [PMID: 28653675]
[http://dx.doi.org/10.1038/pcan.2017.31] [PMID: 28653675]
[16]
Wang W, Bergh A, Damber JE. Morphological transition of proliferative inflammatory atrophy to high-grade intraepithelial neoplasia and cancer in human prostate. Prostate 2009; 69(13): 1378-86.
[http://dx.doi.org/10.1002/pros.20992] [PMID: 19507201]
[http://dx.doi.org/10.1002/pros.20992] [PMID: 19507201]
[17]
Xie DD, Chen YH, Xu S, et al. Low vitamin D status is associated with inflammation in patients with prostate cancer. Oncotarget 2017; 8(13): 22076-85.
[http://dx.doi.org/10.18632/oncotarget.16195] [PMID: 28423553]
[http://dx.doi.org/10.18632/oncotarget.16195] [PMID: 28423553]
[18]
Mrakovčić-Šutić I, Sotošek Tokmadžić V, Ilić Tomaš M, et al. Cross talk between nkt and regulatory t cells (tregs) in prostatic tissue of patients with benign prostatic hyperplasia and prostate cancer. Period Biol 2014; 116: 409-15.
[19]
De Nunzio C, Presicce F, Tubaro A. Inflammatory mediators in the development and progression of benign prostatic hyperplasia. Nat Rev Urol 2016; 13(10): 613-26.
[http://dx.doi.org/10.1038/nrurol.2016.168] [PMID: 27686153]
[http://dx.doi.org/10.1038/nrurol.2016.168] [PMID: 27686153]
[20]
Santoni M, Cheng L, Conti A, et al. Activity and functions of tumor-associated macrophages in prostate carcinogenesis. Eur Urol Suppl 2019; 16: 301-8.
[http://dx.doi.org/10.1016/j.eursup.2017.09.002]
[http://dx.doi.org/10.1016/j.eursup.2017.09.002]
[21]
Cha HR, Lee JH, Hensel JA, et al. Prostate cancer-derived cathelicidin-related antimicrobial peptide facilitates macrophage differentiation and polarization of immature myeloid progenitors to protumorigenic macrophages. Prostate 2016; 76(7): 624-36.
[http://dx.doi.org/10.1002/pros.23155] [PMID: 26856684]
[http://dx.doi.org/10.1002/pros.23155] [PMID: 26856684]
[22]
Hagemann T, Wilson J, Kulbe H, et al. Macrophages induce invasiveness of epithelial cancer cells via NF-kappa B and JNK. J Immunol 2005; 175(2): 1197-205.
[http://dx.doi.org/10.4049/jimmunol.175.2.1197] [PMID: 16002723]
[http://dx.doi.org/10.4049/jimmunol.175.2.1197] [PMID: 16002723]
[23]
Li N, Grivennikov SI, Karin M. The unholy trinity: inflammation, cytokines, and STAT3 shape the cancer microenvironment. Cancer Cell 2011; 19(4): 429-31.
[http://dx.doi.org/10.1016/j.ccr.2011.03.018] [PMID: 21481782]
[http://dx.doi.org/10.1016/j.ccr.2011.03.018] [PMID: 21481782]
[24]
Fang LY, Izumi K, Lai KP, et al. Infiltrating macrophages promote prostate tumorigenesis via modulating androgen receptor-mediated CCL4-STAT3 signaling. Cancer Res 2013; 73(18): 5633-46.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-3228] [PMID: 23878190]
[http://dx.doi.org/10.1158/0008-5472.CAN-12-3228] [PMID: 23878190]
[25]
Maolake A, Izumi K, Shigehara K, et al. Tumor-associated macrophages promote prostate cancer migration through activation of the CCL22-CCR4 axis. Oncotarget 2017; 8(6): 9739-51.
[http://dx.doi.org/10.18632/oncotarget.14185] [PMID: 28039457]
[http://dx.doi.org/10.18632/oncotarget.14185] [PMID: 28039457]
[26]
Lee GT, Kwon SJ, Lee JH, et al. Macrophages induce neuroendocrine differentiation of prostate cancer cells via BMP6-IL6 Loop. Prostate 2011; 71(14): 1525-37.
[http://dx.doi.org/10.1002/pros.21369] [PMID: 21374653]
[http://dx.doi.org/10.1002/pros.21369] [PMID: 21374653]
[27]
Halin S, Rudolfsson SH, Van Rooijen N, Bergh A. Extratumoral macrophages promote tumor and vascular growth in an orthotopic rat prostate tumor model. Neoplasia 2009; 11(2): 177-86.
[http://dx.doi.org/10.1593/neo.81338] [PMID: 19177202]
[http://dx.doi.org/10.1593/neo.81338] [PMID: 19177202]
[28]
Roca H, Varsos ZS, Sud S, Craig MJ, Ying C, Pienta KJ. CCL2 and interleukin-6 promote survival of human CD11b+ peripheral blood mononuclear cells and induce M2-type macrophage polarization. J Biol Chem 2009; 284(49): 34342-54.
[http://dx.doi.org/10.1074/jbc.M109.042671] [PMID: 19833726]
[http://dx.doi.org/10.1074/jbc.M109.042671] [PMID: 19833726]
[29]
Ok Atılgan A, Özdemir BH, Akçay EY, Ataol Demirkan Ö, Tekindal MA, Özkardeş H. Role of tumor-associated macrophages in the Hexim1 and TGFβ/SMAD pathway, and their influence on progression of prostatic adenocarcinoma. Pathol Res Pract 2016; 212(2): 83-92.
[http://dx.doi.org/10.1016/j.prp.2015.10.011] [PMID: 26608417]
[http://dx.doi.org/10.1016/j.prp.2015.10.011] [PMID: 26608417]
[30]
Strasner A, Karin M. Immune infiltration and prostate cancer. Front Oncol 2015; 5: 128.
[http://dx.doi.org/10.3389/fonc.2015.00128] [PMID: 26217583]
[http://dx.doi.org/10.3389/fonc.2015.00128] [PMID: 26217583]
[31]
Zhang Y, Zhang Z, Zhang L, et al. Clinical Implications of Peripheral CD3+CD69+ T-cell and CD8+CD28+ T-cell Proportions in Patients Prior to Radical Prostatectomy. Urol J in press 2020; 17(3): 257-61.
[http://dx.doi.org/10.22037/uj.v0i0.5103] [PMID: 31630384]
[http://dx.doi.org/10.22037/uj.v0i0.5103] [PMID: 31630384]
[32]
Kwek SS, Lewis J, Zhang L, et al. Preexisting levels of cd4 t cells expressing pd-1 are related to overall survival in prostate cancer patients treated with ipilimumab. Cancer Immunol Res 2015; 3(9): 1008-16.
[http://dx.doi.org/10.1158/2326-6066.CIR-14-0227] [PMID: 25968455]
[http://dx.doi.org/10.1158/2326-6066.CIR-14-0227] [PMID: 25968455]
[33]
Evans JD, Morris LK, Zhang H, et al. Prospective immunophenotyping of cd8+ t cells and associated clinical outcomes of patients with oligometastatic prostate cancer treated with metastasis-directed sbrt. Int J Radiat Oncol Biol Phys 2019; 103(1): 229-40.
[http://dx.doi.org/10.1016/j.ijrobp.2018.09.001] [PMID: 30205124]
[http://dx.doi.org/10.1016/j.ijrobp.2018.09.001] [PMID: 30205124]
[34]
Bahig H, Taussky D, Delouya G, et al. Neutrophil count is associated with survival in localized prostate cancer. BMC Cancer 2015; 15: 594.
[http://dx.doi.org/10.1186/s12885-015-1599-9] [PMID: 26292807]
[http://dx.doi.org/10.1186/s12885-015-1599-9] [PMID: 26292807]
[35]
Vidal AC, Howard LE, de Hoedt A, et al. Neutrophil, lymphocyte and platelet counts, and risk of prostate cancer outcomes in white and black men: results from the SEARCH database. Cancer Causes Control 2018; 29(6): 581-8.
[http://dx.doi.org/10.1007/s10552-018-1031-2] [PMID: 29663110]
[http://dx.doi.org/10.1007/s10552-018-1031-2] [PMID: 29663110]
[36]
Minardi D, Scartozzi M, Montesi L, et al. Neutrophil-to-lymphocyte ratio may be associated with the outcome in patients with prostate cancer. Springerplus 2015; 4: 255.
[http://dx.doi.org/10.1186/s40064-015-1036-1] [PMID: 26085975]
[http://dx.doi.org/10.1186/s40064-015-1036-1] [PMID: 26085975]
[37]
Buttigliero C, Tucci M, Vignani F, et al. Chemotherapy-induced neutropenia and outcome in patients with metastatic castration-resistant prostate cancer treated with first-line docetaxel. Clin Genitourin Cancer 2018; 16(4): 318-24.
[http://dx.doi.org/10.1016/j.clgc.2018.05.006] [PMID: 29866495]
[http://dx.doi.org/10.1016/j.clgc.2018.05.006] [PMID: 29866495]
[38]
Scimeca M, Bonfiglio R, Urbano N, et al. Programmed death ligand 1 expression in prostate cancer cells is associated with deep changes of the tumor inflammatory infiltrate composition Urol Oncol 2019; 37(5): 297. e19-.
[http://dx.doi.org/10.1016/j.urolonc.2019.02.013] [PMID: 30827759]
[http://dx.doi.org/10.1016/j.urolonc.2019.02.013] [PMID: 30827759]
[39]
Lindh C, Kis L, Delahunt B, et al. PD-L1 expression and deficient mismatch repair in ductal adenocarcinoma of the prostate. APMIS 2019; 127(8): 554-60.
[http://dx.doi.org/10.1111/apm.12970] [PMID: 31127651]
[http://dx.doi.org/10.1111/apm.12970] [PMID: 31127651]
[40]
Fankhauser CD, Schüffler PJ, Gillessen S, et al. Comprehensive immunohistochemical analysis of PD-L1 shows scarce expression in castration-resistant prostate cancer. Oncotarget 2017; 9(12): 10284-93.
[PMID: 29535806]
[PMID: 29535806]
[41]
Nava Rodrigues D, Rescigno P, Liu D, et al. Immunogenomic analyses associate immunological alterations with mismatch repair defects in prostate cancer. J Clin Invest 2018; 128(10): 4441-53.
[http://dx.doi.org/10.1172/JCI121924] [PMID: 30179225]
[http://dx.doi.org/10.1172/JCI121924] [PMID: 30179225]
[42]
Wu YM, Cieślik M, Lonigro RJ, et al. PCF/SU2C international prostate cancer dream team. inactivation of cdk12 delineates a distinct immunogenic class of advanced prostate cancer. Cell 2018; 173(7): 1770-82.e14.
[http://dx.doi.org/10.1016/j.cell.2018.04.034] [PMID: 29906450]
[http://dx.doi.org/10.1016/j.cell.2018.04.034] [PMID: 29906450]
[43]
Vidotto T, Saggioro FP, Jamaspishvili T, et al. PTEN-deficient prostate cancer is associated with an immunosuppressive tumor microenvironment mediated by increased expression of IDO1 and infiltrating FoxP3+ T regulatory cells. Prostate 2019; 79(9): 969-79.
[http://dx.doi.org/10.1002/pros.23808] [PMID: 30999388]
[http://dx.doi.org/10.1002/pros.23808] [PMID: 30999388]
[44]
Mo RJ, Han ZD, Liang YK, et al. Expression of PD-L1 in tumor-associated nerves correlates with reduced CD8+ tumor-associated lymphocytes and poor prognosis in prostate cancer. Int J Cancer 2019; 144(12): 3099-110.
[http://dx.doi.org/10.1002/ijc.32061] [PMID: 30537104]
[http://dx.doi.org/10.1002/ijc.32061] [PMID: 30537104]
[45]
Petitprez F, Fossati N, Vano Y, et al. PD-L1 Expression and CD8+ t-cell infiltrate are associated with clinical progression in patients with node-positive prostate cancer. Eur Urol Focus 2019; 5(2): 192-6.
[http://dx.doi.org/10.1016/j.euf.2017.05.013] [PMID: 28753812]
[http://dx.doi.org/10.1016/j.euf.2017.05.013] [PMID: 28753812]
[46]
Rekoske BT, Olson BM, McNeel DG. Antitumor vaccination of prostate cancer patients elicits PD-1/PD-L1 regulated antigen-specific immune responses. OncoImmunology 2016; 5(6)e1165377
[http://dx.doi.org/10.1080/2162402X.2016.1165377] [PMID: 27471641]
[http://dx.doi.org/10.1080/2162402X.2016.1165377] [PMID: 27471641]
[47]
Graff JN, Alumkal JJ, Drake CG, et al. Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. Oncotarget 2016; 7(33): 52810-7.
[http://dx.doi.org/10.18632/oncotarget.10547] [PMID: 27429197]
[http://dx.doi.org/10.18632/oncotarget.10547] [PMID: 27429197]
[48]
Raman R, Vaena D. Immunotherapy in metastatic renal cell carcinoma: a comprehensive review. BioMed Res Int 2015.2015367354
[http://dx.doi.org/10.1155/2015/367354] [PMID: 26161397]
[http://dx.doi.org/10.1155/2015/367354] [PMID: 26161397]
[49]
Rittmeyer A, Barlesi F, Waterkamp D, et al. OAK Study Group Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 2017; 389(10066): 255-65.
[http://dx.doi.org/10.1016/S0140-6736(16)32517-X] [PMID: 27979383]
[http://dx.doi.org/10.1016/S0140-6736(16)32517-X] [PMID: 27979383]
[50]
Horn L, Mansfield AS, Szczęsna A, et al. IMpower133 study group. first-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med 2018; 379(23): 2220-9.
[http://dx.doi.org/10.1056/NEJMoa1809064] [PMID: 30280641]
[http://dx.doi.org/10.1056/NEJMoa1809064] [PMID: 30280641]
[51]
Socinski MA, Jotte RM, Cappuzzo F, et al. IMpower150 study group. atezolizumab for first-line treatment of metastatic nonsquamous nsclc. N Engl J Med 2018; 378(24): 2288-301.
[http://dx.doi.org/10.1056/NEJMoa1716948] [PMID: 29863955]
[http://dx.doi.org/10.1056/NEJMoa1716948] [PMID: 29863955]
[52]
Powles T, Durán I, van der Heijden MS, et al. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet 2018; 391(10122): 748-57.
[http://dx.doi.org/10.1016/S0140-6736(17)33297-X] [PMID: 29268948]
[http://dx.doi.org/10.1016/S0140-6736(17)33297-X] [PMID: 29268948]
[53]
Schmid P, Adams S, Rugo HS, et al. IMpassion130 Trial Investigators. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med 2018; 379(22): 2108-21.
[http://dx.doi.org/10.1056/NEJMoa1809615] [PMID: 30345906]
[http://dx.doi.org/10.1056/NEJMoa1809615] [PMID: 30345906]
[54]
Rini BI, Powles T, Atkins MB, et al. IMmotion151 Study Group. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet 2019; 393(10189): 2404-15.
[http://dx.doi.org/10.1016/S0140-6736(19)30723-8] [PMID: 31079938]
[http://dx.doi.org/10.1016/S0140-6736(19)30723-8] [PMID: 31079938]
[55]
Kaufman HL, Russell J, Hamid O, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol 2016; 17(10): 1374-85.
[http://dx.doi.org/10.1016/S1470-2045(16)30364-3] [PMID: 27592805]
[http://dx.doi.org/10.1016/S1470-2045(16)30364-3] [PMID: 27592805]
[56]
Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2019; 380(12): 1103-15.
[http://dx.doi.org/10.1056/NEJMoa1816047] [PMID: 30779531]
[http://dx.doi.org/10.1056/NEJMoa1816047] [PMID: 30779531]
[57]
Antonia SJ, Villegas A, Daniel D, et al. PACIFIC investigators durvalumab after chemoradiotherapy in stage iii non-small-cell lung cancer. N Engl J Med 2017; 377(20): 1919-29.
[http://dx.doi.org/10.1056/NEJMoa1709937] [PMID: 28885881]
[http://dx.doi.org/10.1056/NEJMoa1709937] [PMID: 28885881]
[58]
Rijnders M, de Wit R, Boormans JL, Lolkema MPJ, van der Veldt AAM. Systematic review of immune checkpoint inhibition in urological cancers. Eur Urol 2017; 72(3): 411-23.
[http://dx.doi.org/10.1016/j.eururo.2017.06.012] [PMID: 28645491]
[http://dx.doi.org/10.1016/j.eururo.2017.06.012] [PMID: 28645491]
[59]
Dudek AZ, Liu LC, Alva AS, Stein M, Gupta S, Albany C, et al. Phase ib and phase II studies of pembrolizumab (P) with bevacizumab (B) for the treatment of metastatic renal cell carcinoma (RCC): BTCRC-GU14-003. J Clin Oncol 2018; 3615: 4558-8.
[60]
Chowdhury S, McDermott DF, Voss MH, et al. A phase I/II study to assess the safety and efficacy of pazopanib (PAZ) and pembrolizumab (PEM) in patients (pts) with advanced renal cell carcinoma (aRCC). J Clin Oncol 2017; 1515: 4506-6.
[61]
Hammers HJ, Plimack ER, Infante JR, et al. Safety and Efficacy of Nivolumab in Combination With Ipilimumab in Metastatic Renal Cell Carcinoma: The CheckMate 016 Study. J Clin Oncol 2017; 35(34): 3851-8.
[http://dx.doi.org/10.1200/JCO.2016.72.1985] [PMID: 28678668]
[http://dx.doi.org/10.1200/JCO.2016.72.1985] [PMID: 28678668]
[62]
Santoni M, Scarpelli M, Mazzucchelli R, et al. Current histopathologic and molecular characterisations of prostate cancer: towards individualised prognosis and therapies. Eur Urol 2016; 69(2): 186-90.
[http://dx.doi.org/10.1016/j.eururo.2015.05.041] [PMID: 26070514]
[http://dx.doi.org/10.1016/j.eururo.2015.05.041] [PMID: 26070514]
[63]
Cimadamore A, Santoni M, Massari F, et al. Microbiome and Cancers, With Focus on Genitourinary Tumors. Front Oncol 2019; 9: 178.
[http://dx.doi.org/10.3389/fonc.2019.00178] [PMID: 30972292]
[http://dx.doi.org/10.3389/fonc.2019.00178] [PMID: 30972292]
[64]
Bersanelli M, Santoni M, Ticinesi A, Buti S. The urinary microbiome and anticancer immunotherapy: the potentially hidden role of unculturable microbes. Target Oncol 2019; 14(3): 247-52.
[http://dx.doi.org/10.1007/s11523-019-00643-7] [PMID: 31073691]
[http://dx.doi.org/10.1007/s11523-019-00643-7] [PMID: 31073691]
[65]
Shrestha E, White JR, Yu SH, et al. Profiling the Urinary Microbiome in Men with Positive versus Negative Biopsies for Prostate Cancer. J Urol 2018; 199(1): 161-71.
[http://dx.doi.org/10.1016/j.juro.2017.08.001] [PMID: 28797714]
[http://dx.doi.org/10.1016/j.juro.2017.08.001] [PMID: 28797714]
[66]
Massari F, Mollica V, Di Nunno V, et al. The human microbiota and prostate cancer: friend or foe? Cancers (Basel) 2019; 11(4)E459
[http://dx.doi.org/10.3390/cancers11040459] [PMID: 30935126]
[http://dx.doi.org/10.3390/cancers11040459] [PMID: 30935126]
[67]
Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science 2018; 359(6371): 91-7.
[http://dx.doi.org/10.1126/science.aan3706] [PMID: 29097494]
[http://dx.doi.org/10.1126/science.aan3706] [PMID: 29097494]
[68]
Santoni M, Piva F, Conti A, et al. Re: Gut microbiome influences efficacy of pd-1-based immunotherapy against epithelial tumors. Eur Urol 2018; 74(4): 521-2.
[http://dx.doi.org/10.1016/j.eururo.2018.05.033] [PMID: 29891391]
[http://dx.doi.org/10.1016/j.eururo.2018.05.033] [PMID: 29891391]
[69]
Strauss J, Heery CR, Schlom J, et al. Phase i trial of m7824 (msb0011359c), a bifunctional fusion protein targeting pd-l1 and tgfβ, in advanced solid tumors. Clin Cancer Res 2018; 24(6): 1287-95.
[http://dx.doi.org/10.1158/1078-0432.CCR-17-2653] [PMID: 29298798]
[http://dx.doi.org/10.1158/1078-0432.CCR-17-2653] [PMID: 29298798]
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