Generic placeholder image

Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Review Article

Research Progress of PD 1/PD L1 Inhibitors in the Treatment of Urological Tumors

Author(s): Lv Han, Yang Meng and Zhu Jianguo*

Volume 24, Issue 11, 2024

Published on: 02 February, 2024

Page: [1104 - 1115] Pages: 12

DOI: 10.2174/0115680096278251240108152600

Abstract

Immune checkpoint inhibitors (ICIs) offer significant advantages for the treatment of urologic tumors, enhancing the immune function of anti-tumor T cells by inhibiting PD-1 and PDL1 binding. They have been shown to be well tolerated and remarkably effective in clinical practice, offering hope to many patients who are not well treated with conventional drugs. Clinical trials in recent years have shown that anti-PD-1 and PD-L1 antibodies have good efficacy and safety in the treatment of urologic tumors. These antibodies can be applied to a variety of urologic tumors, such as bladder cancer, renal cell carcinoma, and prostate cancer. They have been approved for the first-line treatment or as an option for follow-up therapy. By blocking the PD-1/PD-L1 signaling pathway, ICIs can release immune functions that are suppressed by tumor cells and enhance T-cell killing, thereby inhibiting tumor growth and metastasis. This therapeutic approach has achieved encouraging efficacy and improved survival for many patients. Although ICIs have shown remarkable results in the treatment of urologic tumors, some problems remain, such as drug resistance and adverse effects in some patients. Therefore, further studies remain important to optimize treatment strategies and improve clinical response in patients. In conclusion, PD-1/PD-L1 signaling pathway blockers have important research advances for the treatment of urologic tumors. Their emergence brings new hope for patients who have poor outcomes with traditional drug therapy and provides new options for immunotherapy of urologic tumors. The purpose of this article is to review the research progress of PD-1 and PD-L1 signaling pathway blockers in urologic tumors in recent years.

Graphical Abstract

[1]
Cao, M.; Li, H.; Sun, D.; He, S.; Yan, X.; Yang, F.; Zhang, S.; Xia, C.; Lei, L.; Peng, J.; Chen, W. Current cancer burden in China: Epidemiology, etiology, and prevention. Cancer Biol. Med., 2022, 19(8), 1121-1138.
[http://dx.doi.org/10.20892/j.issn.2095-3941.2022.0231] [PMID: 36069534]
[2]
Wang, H.; Duan, J.; Wu, S.; Chen, J.; Lei, Z.; Lu, T. Progress of PD-1/PD-L1 blockers in immunotherapy of urologic malignancies. J. Minim. Invasive Urol., 2017, (3), 6.
[3]
Tichet, M.; Wullschleger, S.; Chryplewicz, A.; Fournier, N.; Marcone, R.; Kauzlaric, A.; Homicsko, K.; Deak, L.C.; Umaña, P.; Klein, C.; Hanahan, D. Bispecific PD1-IL2v and anti-PD-L1 break tumor immunity resistance by enhancing stem-like tumor-reactive CD8+ T cells and reprogramming macrophages. Immunity, 2023, 56(1), 162-179.e6.
[http://dx.doi.org/10.1016/j.immuni.2022.12.006] [PMID: 36630914]
[4]
Bagchi, S.; Yuan, R.; Engleman, E.G. Immune checkpoint inhibitors for the treatment of cancer: Clinical impact and mechanisms of response and resistance. Annu. Rev. Pathol., 2021, 16(1), 223-249.
[http://dx.doi.org/10.1146/annurev-pathol-042020-042741] [PMID: 33197221]
[5]
Yap, T.A.; Parkes, E.E.; Peng, W.; Moyers, J.T.; Curran, M.A.; Tawbi, H.A. Development of immunotherapy combination strategies in cancer. Cancer Discov., 2021, 11(6), 1368-1397.
[http://dx.doi.org/10.1158/2159-8290.CD-20-1209] [PMID: 33811048]
[6]
Yang , XL.; Tian , JQ. Research progress of PD-1/PD-L1 inhibitors for bladder cancer. Med. Rev., 2019, 25(17), 7.
[7]
Tang , Q.; Chen, Y.; Li, Y. The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers. Front Immunol., 2022, 13, 964442.
[8]
Liu, J.; Chen, Z.; Li, Y.; Zhao, W.; Wu, J.; Zhang, Z. PD-1/PD-L1 checkpoint inhibitors in tumor immunotherapy. Front. Pharmacol., 2021, 12, 731798.
[http://dx.doi.org/10.3389/fphar.2021.731798] [PMID: 34539412]
[9]
Nishimura, H.; Nose, M.; Hiai, H.; Minato, N.; Honjo, T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity, 1999, 11(2), 141-151.
[http://dx.doi.org/10.1016/S1074-7613(00)80089-8] [PMID: 10485649]
[10]
Ishida, Y.; Agata, Y.; Shibahara, K.; Honjo, T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J., 1992, 11(11), 3887-3895.
[http://dx.doi.org/10.1002/j.1460-2075.1992.tb05481.x] [PMID: 1396582]
[11]
Agata, Y.; Kawasaki, A.; Nishimura, H.; Ishida, Y.; Tsubat, T.; Yagita, H.; Honjo, T. Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int. Immunol., 1996, 8(5), 765-772.
[http://dx.doi.org/10.1093/intimm/8.5.765] [PMID: 8671665]
[12]
Iwai, Y.; Ishida, M.; Tanaka, Y.; Okazaki, T.; Honjo, T.; Minato, N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc. Natl. Acad. Sci. USA, 2002, 99(19), 12293-12297.
[http://dx.doi.org/10.1073/pnas.192461099] [PMID: 12218188]
[13]
Brahmer, J.R.; Tykodi, S.S.; Chow, L.Q.M.; Hwu, W.J.; Topalian, S.L.; Hwu, P.; Drake, C.G.; Camacho, L.H.; Kauh, J.; Odunsi, K.; Pitot, H.C.; Hamid, O.; Bhatia, S.; Martins, R.; Eaton, K.; Chen, S.; Salay, T.M.; Alaparthy, S.; Grosso, J.F.; Korman, A.J.; Parker, S.M.; Agrawal, S.; Goldberg, S.M.; Pardoll, D.M.; Gupta, A.; Wigginton, J.M. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N. Engl. J. Med., 2012, 366(26), 2455-2465.
[http://dx.doi.org/10.1056/NEJMoa1200694] [PMID: 22658128]
[14]
Yi, M.; Zheng, X.; Niu, M.; Zhu, S.; Ge, H.; Wu, K. Combination strategies with PD-1/PD-L1 blockade: Current advances and future directions. Mol. Cancer, 2022, 21(1), 28.
[http://dx.doi.org/10.1186/s12943-021-01489-2] [PMID: 35062949]
[15]
Zhuang, Y.; Liu, C.; Liu, J.; Li, G. Resistance mechanism of PD-1/PD-L1 blockade in the cancer-immunity cycle. OncoTargets Ther., 2020, 13, 83-94.
[http://dx.doi.org/10.2147/OTT.S239398] [PMID: 32021257]
[16]
Sharpe, A.H.; Pauken, K.E. The diverse functions of the PD1 inhibitory pathway. Nat. Rev. Immunol., 2018, 18(3), 153-167.
[http://dx.doi.org/10.1038/nri.2017.108] [PMID: 28990585]
[17]
O’Neill, R.E.; Cao, X. Co-stimulatory and co-inhibitory pathways in cancer immunotherapy. Adv. Cancer Res., 2019, 143, 145-194.
[http://dx.doi.org/10.1016/bs.acr.2019.03.003] [PMID: 31202358]
[18]
Schütz, F.; Stefanovic, S.; Mayer, L.; von Au, A.; Domschke, C.; Sohn, C. PD-1/PD-L1 pathway in breast cancer. Oncol. Res. Treat., 2017, 40(5), 294-297.
[http://dx.doi.org/10.1159/000464353] [PMID: 28346916]
[19]
Ribas, A.; Wolchok, J.D. Cancer immunotherapy using checkpoint blockade. Science, 2018, 359(6382), 1350-1355.
[http://dx.doi.org/10.1126/science.aar4060] [PMID: 29567705]
[20]
Liu, C.; Yang, M.; Zhang, D.; Chen, M.; Zhu, D. Clinical cancer immunotherapy: Current progress and prospects. Front. Immunol., 2022, 13, 961805.
[http://dx.doi.org/10.3389/fimmu.2022.961805] [PMID: 36304470]
[21]
Dong, H.; Strome, S.E.; Salomao, D.R.; Tamura, H.; Hirano, F.; Flies, D.B.; Roche, P.C.; Lu, J.; Zhu, G.; Tamada, K.; Lennon, V.A.; Celis, E.; Chen, L. Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat. Med., 2002, 8(8), 793-800.
[http://dx.doi.org/10.1038/nm730] [PMID: 12091876]
[22]
Singh, S.; Hassan, D.; Aldawsari, H.M.; Molugulu, N.; Shukla, R.; Kesharwani, P. Immune checkpoint inhibitors: A promising anticancer therapy. Drug Discov. Today, 2020, 25(1), 223-229.
[http://dx.doi.org/10.1016/j.drudis.2019.11.003] [PMID: 31738877]
[23]
Wei, G.; Zhang, H.; Zhao, H.; Wang, J.; Wu, N.; Li, L.; Wu, J.; Zhang, D. Emerging immune checkpoints in the tumor microenvironment: Implications for cancer immunotherapy. Cancer Lett., 2021, 511, 68-76.
[http://dx.doi.org/10.1016/j.canlet.2021.04.021] [PMID: 33957184]
[24]
Ngiow, S.F.; von Scheidt, B.; Akiba, H.; Yagita, H.; Teng, M.W.L.; Smyth, M.J. Anti-TIM3 antibody promotes T cell IFN-γ-mediated antitumor immunity and suppresses established tumors. Cancer Res., 2011, 71(10), 3540-3551.
[http://dx.doi.org/10.1158/0008-5472.CAN-11-0096] [PMID: 21430066]
[25]
Fadel, F.; Karoui, K.E.; Knebelmann, B. Anti-CTLA4 antibody-induced lupus nephritis. N. Engl. J. Med., 2009, 361(2), 211-212.
[http://dx.doi.org/10.1056/NEJMc0904283] [PMID: 19587352]
[26]
Boutros, C.; Tarhini, A.; Routier, E.; Lambotte, O.; Ladurie, F.L.; Carbonnel, F.; Izzeddine, H.; Marabelle, A.; Champiat, S.; Berdelou, A.; Lanoy, E.; Texier, M.; Libenciuc, C.; Eggermont, A.M.M.; Soria, J.C.; Mateus, C.; Robert, C. Safety profiles of anti-CTLA-4 and anti-PD-1 antibodies alone and in combination. Nat. Rev. Clin. Oncol., 2016, 13(8), 473-486.
[http://dx.doi.org/10.1038/nrclinonc.2016.58] [PMID: 27141885]
[27]
Crocetto, F.; Russo, G.; Di Zazzo, E.; Pisapia, P.; Mirto, B.F.; Palmieri, A.; Pepe, F.; Bellevicine, C.; Russo, A.; La Civita, E.; Terracciano, D.; Malapelle, U.; Troncone, G.; Barone, B. Liquid biopsy in prostate cancer management—current challenges and future perspectives. Cancers, 2022, 14(13), 3272.
[http://dx.doi.org/10.3390/cancers14133272] [PMID: 35805043]
[28]
Katongole, P.; Sande, O.J.; Reynolds, S.J.; Joloba, M.; Kajumbula, H.; Kalungi, S.; Ssebambulidde, K.; Nakimuli, C.; Atuheirwe, M.; Orem, J.; Niyonzima, N. Soluble programmed death-ligand 1 (sPD-L1) is elevated in aggressive prostate cancer disease among african men. Oncol. Ther., 2022, 10(1), 185-193.
[http://dx.doi.org/10.1007/s40487-022-00184-6] [PMID: 35128628]
[29]
Zhou, X.; Zou, L.; Liao, H.; Luo, J.; Yang, T.; Wu, J.; Chen, W.; Wu, K.; Cen, S.; Lv, D.; Shu, F.; Yang, Y.; Li, C.; Li, B.; Mao, X. Abrogation of HnRNP L enhances anti-PD-1 therapy efficacy via diminishing PD-L1 and promoting CD8+ T cell-mediated ferroptosis in castration-resistant prostate cancer. Acta Pharm. Sin. B, 2022, 12(2), 692-707.
[http://dx.doi.org/10.1016/j.apsb.2021.07.016] [PMID: 35256940]
[30]
Hansen, A.R.; Massard, C.; Ott, P.A.; Haas, N.B.; Lopez, J.S.; Ejadi, S.; Wallmark, J.M.; Keam, B.; Delord, J.P.; Aggarwal, R.; Gould, M.; Yang, P.; Keefe, S.M.; Piha-Paul, S.A. Pembrolizumab for advanced prostate adenocarcinoma: Findings of the KEYNOTE-028 study. Ann. Oncol., 2018, 29(8), 1807-1813.
[http://dx.doi.org/10.1093/annonc/mdy232] [PMID: 29992241]
[31]
Ma, Z.; Zhang, W.; Dong, B.; Xin, Z.; Ji, Y.; Su, R.; Shen, K.; Pan, J.; Wang, Q.; Xue, W. Docetaxel remodels prostate cancer immune microenvironment and enhances checkpoint inhibitor-based immunotherapy. Theranostics, 2022, 12(11), 4965-4979.
[http://dx.doi.org/10.7150/thno.73152] [PMID: 35836810]
[32]
Han, H.J.; Li, Y.R.; Roach, M., III; Aggarwal, R. Dramatic response to combination pembrolizumab and radiation in metastatic castration resistant prostate cancer. Ther. Adv. Med. Oncol., 2020, 12
[http://dx.doi.org/10.1177/1758835920936084] [PMID: 32922519]
[33]
Shi, X.; Zhang, X.; Li, J.; Zhao, H.; Mo, L.; Shi, X.; Hu, Z.; Gao, J.; Tan, W. PD-1/PD-L1 blockade enhances the efficacy of SA-GM-CSF surface-modified tumor vaccine in prostate cancer. Cancer Lett., 2017, 406, 27-35.
[http://dx.doi.org/10.1016/j.canlet.2017.07.029] [PMID: 28797844]
[34]
Abida, W.; Cheng, M.L.; Armenia, J.; Middha, S.; Autio, K.A.; Vargas, H.A.; Rathkopf, D.; Morris, M.J.; Danila, D.C.; Slovin, S.F.; Carbone, E.; Barnett, E.S.; Hullings, M.; Hechtman, J.F.; Zehir, A.; Shia, J.; Jonsson, P.; Stadler, Z.K.; Srinivasan, P.; Laudone, V.P.; Reuter, V.; Wolchok, J.D.; Socci, N.D.; Taylor, B.S.; Berger, M.F.; Kantoff, P.W.; Sawyers, C.L.; Schultz, N.; Solit, D.B.; Gopalan, A.; Scher, H.I. Analysis of the prevalence of microsatellite instability in prostate cancer and response to immune checkpoint blockade. JAMA Oncol., 2019, 5(4), 471-478.
[http://dx.doi.org/10.1001/jamaoncol.2018.5801] [PMID: 30589920]
[35]
Deng, G.; He, J.; Huang, Q.; Li, T.; Huang, Z.; Gao, S.; Xu, J.; Wang, T.; Di, J. Ibrutinib inhibits BTK signaling in tumor-infiltrated B cells and amplifies antitumor immunity by PD-1 checkpoint blockade for metastatic prostate cancer. Cancers, 2023, 15(8), 2356.
[http://dx.doi.org/10.3390/cancers15082356] [PMID: 37190284]
[36]
Dong, B-J.; Du, X-X.; Dong, Y-H.; Zhu, H-J.; Fei, X-C.; Gong, Y-M.; Xia, B-B.; Wu, F.; Wang, J-Y.; Liu, J-Z.; Fan, L-C.; Wang, Y-Q.; Dong, L.; Zhu, Y-J.; Pan, J-H.; Xue, W. PD-1 inhibitor plus anlotinib for metastatic castration-resistant prostate cancer: A real-world study. Asian J. Androl., 2023, 25(2), 179-183.
[http://dx.doi.org/10.4103/aja2022102] [PMID: 36537376]
[37]
Hong, X.; Zhang, Y.; Chi, Z. Efficacy and safety of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) checkpoint inhibitors in patients with metastatic castration-resistant prostate cancer: A systematic review and meta-analysis. Clin. Oncol., 2023.
[PMID: 37993317]
[38]
Crane, C.A.; Panner, A.; Murray, J.C.; Wilson, S.P.; Xu, H.; Chen, L.; Simko, J.P.; Waldman, F.M.; Pieper, R.O.; Parsa, A.T. PI(3) kinase is associated with a mechanism of immunoresistance in breast and prostate cancer. Oncogene, 2009, 28(2), 306-312.
[http://dx.doi.org/10.1038/onc.2008.384] [PMID: 18850006]
[39]
Gillette, C.M.; Yette, G.A.; Cramer, S.D.; Graham, L.S. Management of advanced prostate cancer in the precision oncology era. Cancers, 2023, 15(9), 2552.
[http://dx.doi.org/10.3390/cancers15092552] [PMID: 37174018]
[40]
Bouchelouche, K. PET/CT in bladder cancer: An update. Semin. Nucl. Med., 2022, 52(4), 475-485.
[http://dx.doi.org/10.1053/j.semnuclmed.2021.12.004] [PMID: 34996595]
[41]
Chen, R.; Zhou, X.; Liu, J.; Huang, G. Relationship between the expression of PD-1/PD-L1 and 18F-FDG uptake in bladder cancer. Eur. J. Nucl. Med. Mol. Imaging, 2019, 46(4), 848-854.
[http://dx.doi.org/10.1007/s00259-018-4208-8] [PMID: 30627815]
[42]
Kawahara, T.; Ishiguro, Y.; Ohtake, S.; Kato, I.; Ito, Y.; Ito, H.; Makiyama, K.; Kondo, K.; Miyoshi, Y.; Yumura, Y.; Hayashi, N.; Hasumi, H.; Osaka, K.; Muraoka, K.; Izumi, K.; Teranishi, J.; Uemura, H.; Yao, M.; Nakaigawa, N. PD-1 and PD-L1 are more highly expressed in high-grade bladder cancer than in low-grade cases: PD-L1 might function as a mediator of stage progression in bladder cancer. BMC Urol., 2018, 18(1), 97.
[http://dx.doi.org/10.1186/s12894-018-0414-8] [PMID: 30400941]
[43]
Flores-Martín, J.F.; Perea, F.; Exposito-Ruiz, M.; Carretero, F.J.; Rodriguez, T.; Villamediana, M.; Ruiz-Cabello, F.; Garrido, F.; Cózar-Olmo, J.M.; Aptsiauri, N. A combination of positive tumor HLA-I and negative PD-L1 expression provides an immune rejection mechanism in bladder cancer. Ann. Surg. Oncol., 2019, 26(8), 2631-2639.
[http://dx.doi.org/10.1245/s10434-019-07371-2] [PMID: 31011905]
[44]
Lim, S.; Park, J.H.; Chang, H. Enhanced anti-tumor immunity of vaccine combined with anti-PD-1 antibody in a murine bladder cancer model. Investig. Clin. Urol., 2023, 64(1), 74-81.
[http://dx.doi.org/10.4111/icu.20220031] [PMID: 36629068]
[45]
Zhao, Z.; Liu, S.; Sun, R.; Zhu, W.; Zhang, Y.; Liu, T.; Li, T.; Jiang, N.; Guo, H.; Yang, R. The combination of oxaliplatin and anti-PD-1 inhibitor promotes immune cells infiltration and enhances anti-tumor effect of PD-1 blockade in bladder cancer. Front. Immunol., 2023, 14, 1085476.
[http://dx.doi.org/10.3389/fimmu.2023.1085476] [PMID: 36960067]
[46]
Massard, C.; Gordon, M.S.; Sharma, S.; Rafii, S.; Wainberg, Z.A.; Luke, J.; Curiel, T.J.; Colon-Otero, G.; Hamid, O.; Sanborn, R.E.; O’Donnell, P.H.; Drakaki, A.; Tan, W.; Kurland, J.F.; Rebelatto, M.C.; Jin, X.; Blake-Haskins, J.A.; Gupta, A.; Segal, N.H. Safety and efficacy of durvalumab (MEDI4736), an anti–programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J. Clin. Oncol., 2016, 34(26), 3119-3125.
[http://dx.doi.org/10.1200/JCO.2016.67.9761] [PMID: 27269937]
[47]
Apolo, A.B.; Infante, J.R.; Balmanoukian, A.; Patel, M.R.; Wang, D.; Kelly, K.; Mega, A.E.; Britten, C.D.; Ravaud, A.; Mita, A.C.; Safran, H.; Stinchcombe, T.E.; Srdanov, M.; Gelb, A.B.; Schlichting, M.; Chin, K.; Gulley, J.L. Avelumab, an anti–programmed death-ligand 1 antibody, in patients with refractory metastatic urothelial carcinoma: Results from a multicenter, phase Ib study. J. Clin. Oncol., 2017, 35(19), 2117-2124.
[http://dx.doi.org/10.1200/JCO.2016.71.6795] [PMID: 28375787]
[48]
García-Perdomo, H.A.; Sánchez, A.L.; Spiess, P.E. Immune checkpoints inhibitors in the management of high-risk non-muscle-invasive bladder cancer. A scoping review. Urol. Oncol., 2022, 40(9), 409.e1-409.e8.
[http://dx.doi.org/10.1016/j.urolonc.2022.02.003] [PMID: 35232680]
[49]
Woodcock, V.K.; Chen, J.L.; Purshouse, K.; Butcher, C.; Collins, L.; Haddon, C.; Verrall, G.; Elhussein, L.; Roberts, C.; Tarlton, A.; Rei, M.; Napolitani, G.; Salio, M.; Middleton, M.R.; Cerundolo, V.; Crew, J.; Protheroe, A.S. PemBla: A phase 1 study of intravesical pembrolizumab in recurrent non-muscle-invasive bladder cancer. BJUI Compass, 2023, 4(3), 322-330.
[http://dx.doi.org/10.1002/bco2.220] [PMID: 37025470]
[50]
Xu, C.; Zou, W.; Zhang, L.; Xu, R.; Li, Y.; Feng, Y.; Zhao, R.; Wang, Y.; Liu, X.; Wang, J. Real-world retrospective study of immune checkpoint inhibitors in combination with radiotherapy or chemoradiotherapy as a bladder-sparing treatment strategy for muscle-invasive bladder urothelial cancer. Front. Immunol., 2023, 14, 1162580.
[http://dx.doi.org/10.3389/fimmu.2023.1162580] [PMID: 37283762]
[51]
Li, T.; Hu, W.; Jin, L.; Yin, X.; Kang, D.; Piao, L. Case Report: PD-L1-negative advanced bladder cancer effectively treated with anlotinib and tislelizumab: A report of two cases. Front. Oncol., 2023, 13, 1164368.
[http://dx.doi.org/10.3389/fonc.2023.1164368] [PMID: 37124509]
[52]
Bellmunt, J.; de Wit, R.; Vaughn, D.J.; Fradet, Y.; Lee, J.L.; Fong, L.; Vogelzang, N.J.; Climent, M.A.; Petrylak, D.P.; Choueiri, T.K.; Necchi, A.; Gerritsen, W.; Gurney, H.; Quinn, D.I.; Culine, S.; Sternberg, C.N.; Mai, Y.; Poehlein, C.H.; Perini, R.F.; Bajorin, D.F. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N. Engl. J. Med., 2017, 376(11), 1015-1026.
[http://dx.doi.org/10.1056/NEJMoa1613683] [PMID: 28212060]
[53]
Flaig, T.W.; Spiess, P.E.; Abern, M.; Agarwal, N.; Bangs, R.; Boorjian, S.A.; Buyyounouski, M.K.; Chan, K.; Chang, S.; Friedlander, T.; Greenberg, R.E.; Guru, K.A.; Herr, H.W.; Hoffman-Censits, J.; Kishan, A.; Kundu, S.; Lele, S.M.; Mamtani, R.; Margulis, V.; Mian, O.Y.; Michalski, J.; Montgomery, J.S.; Nandagopal, L.; Pagliaro, L.C.; Parikh, M.; Patterson, A.; Plimack, E.R.; Pohar, K.S.; Preston, M.A.; Richards, K.; Sexton, W.J.; Siefker-Radtke, A.O.; Tollefson, M.; Tward, J.; Wright, J.L.; Dwyer, M.A.; Cassara, C.J.; Gurski, L.A. NCCN guidelines® insights: Bladder cancer, version 2.2022. J. Natl. Compr. Canc. Netw., 2022, 20(8), 866-878.
[http://dx.doi.org/10.6004/jnccn.2022.0041] [PMID: 35948037]
[54]
Han, S.; Ji, Z.; Jiang, J.; Fan, X.; Ma, Q.; Hu, L.; Zhang, W.; Ping, H.; Wang, J.; Xu, W.; Shi, B.; Wang, W.; Wang, H.; Wang, H.; Chen, S.; Hu, H.; Guo, J.; Zhang, S.; Jiang, S.; Zhou, Q.; Xing, N. Neoadjuvant therapy with camrelizumab plus gemcitabine and cisplatin for patients with muscle-invasive bladder cancer: A multi-center, single-arm, phase 2 study. Cancer Med., 2023, 12(11), 12106-12117.
[http://dx.doi.org/10.1002/cam4.5900] [PMID: 37021811]
[55]
Joshi, M.; Tuanquin, L.; Zhu, J.; Walter, V.; Schell, T.; Kaag, M.; Kilari, D.; Liao, J.; Holder, S.L.; Emamekhoo, H.; Sankin, A.; Merrill, S.; Zheng, H.; Warrick, J.; Hauke, R.; Gartrel, B.; Stein, M.; Drabick, J.; Degraff, D.J.; Zakharia, Y. Concurrent durvalumab and radiation therapy (DUART) followed by adjuvant durvalumab in patients with localized urothelial cancer of bladder: Results from phase II study, BTCRC-GU15-023. J. Immunother. Cancer, 2023, 11(2), e006551.
[http://dx.doi.org/10.1136/jitc-2022-006551] [PMID: 36822667]
[56]
Kubiliute, R.; Jarmalaite, S. Epigenetic biomarkers of renal cell carcinoma for liquid biopsy tests. Int. J. Mol. Sci., 2021, 22(16), 8846.
[http://dx.doi.org/10.3390/ijms22168846] [PMID: 34445557]
[57]
Hsieh, J.J.; Purdue, M.P.; Signoretti, S.; Swanton, C.; Albiges, L.; Schmidinger, M.; Heng, D.Y.; Larkin, J.; Ficarra, V. Renal cell carcinoma. Nat. Rev. Dis. Primers, 2017, 3(1), 17009.
[http://dx.doi.org/10.1038/nrdp.2017.9] [PMID: 28276433]
[58]
McKay, R.R.; Bossé, D.; Choueiri, T.K. Evolving systemic treatment landscape for patients with advanced renal cell carcinoma. J. Clin. Oncol., 2018, 36(36), 3615-3623.
[http://dx.doi.org/10.1200/JCO.2018.79.0253] [PMID: 30372392]
[59]
McDermott, D.F.; Cheng, S.C.; Signoretti, S.; Margolin, K.A.; Clark, J.I.; Sosman, J.A.; Dutcher, J.P.; Logan, T.F.; Curti, B.D.; Ernstoff, M.S.; Appleman, L.; Wong, M.K.K.; Khushalani, N.I.; Oleksowicz, L.; Vaishampayan, U.N.; Mier, J.W.; Panka, D.J.; Bhatt, R.S.; Bailey, A.S.; Leibovich, B.C.; Kwon, E.D.; Kabbinavar, F.F.; Belldegrun, A.S.; Figlin, R.A.; Pantuck, A.J.; Regan, M.M.; Atkins, M.B. The high-dose aldesleukin “select” trial: A trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. Clin. Cancer Res., 2015, 21(3), 561-568.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-1520] [PMID: 25424850]
[60]
Sharma, P.; Allison, J.P. The future of immune checkpoint therapy. Science, 2015, 348(6230), 56-61.
[http://dx.doi.org/10.1126/science.aaa8172] [PMID: 25838373]
[61]
Wu, X.; Gu, Z.; Chen, Y.; Chen, B.; Chen, W.; Weng, L.; Liu, X. Application of PD-1 blockade in cancer immunotherapy. Comput. Struct. Biotechnol. J., 2019, 17, 661-674.
[http://dx.doi.org/10.1016/j.csbj.2019.03.006] [PMID: 31205619]
[62]
Jahangir, M.; Yazdani, O.; Kahrizi, M.S.; Soltanzadeh, S.; Javididashtbayaz, H.; Mivefroshan, A.; Ilkhani, S.; Esbati, R. Clinical potential of PD-1/PD-L1 blockade therapy for renal cell carcinoma (RCC): A rapidly evolving strategy. Cancer Cell Int., 2022, 22(1), 401.
[http://dx.doi.org/10.1186/s12935-022-02816-3] [PMID: 36510217]
[63]
Mazza, C.; Escudier, B.; Albiges, L. Nivolumab in renal cell carcinoma: Latest evidence and clinical potential. Ther. Adv. Med. Oncol., 2017, 9(3), 171-181.
[http://dx.doi.org/10.1177/1758834016679942] [PMID: 28344662]
[64]
Choueiri, T.K.; Powles, T.; Burotto, M.; Escudier, B.; Bourlon, M.T.; Zurawski, B.; Oyervides Juárez, V.M.; Hsieh, J.J.; Basso, U.; Shah, A.Y.; Suárez, C.; Hamzaj, A.; Goh, J.C.; Barrios, C.; Richardet, M.; Porta, C.; Kowalyszyn, R.; Feregrino, J.P.; Żołnierek, J.; Pook, D.; Kessler, E.R.; Tomita, Y.; Mizuno, R.; Bedke, J.; Zhang, J.; Maurer, M.A.; Simsek, B.; Ejzykowicz, F.; Schwab, G.M.; Apolo, A.B.; Motzer, R.J. Nivolumab plus cabozantinib versus sunitinib for advanced renal-cell carcinoma. N. Engl. J. Med., 2021, 384(9), 829-841.
[http://dx.doi.org/10.1056/NEJMoa2026982] [PMID: 33657295]
[65]
Tannir, N.M.; Signoretti, S.; Choueiri, T.K.; McDermott, D.F.; Motzer, R.J.; Flaifel, A.; Pignon, J.C.; Ficial, M.; Frontera, O.A.; George, S.; Powles, T.; Donskov, F.; Harrison, M.R.; Barthélémy, P.; Tykodi, S.S.; Kocsis, J.; Ravaud, A.; Rodriguez-Cid, J.R.; Pal, S.K.; Murad, A.M.; Ishii, Y.; Saggi, S.S.; McHenry, M.B.; Rini, B.I. Efficacy and safety of nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma. Clin. Cancer Res., 2021, 27(1), 78-86.
[http://dx.doi.org/10.1158/1078-0432.CCR-20-2063] [PMID: 32873572]
[66]
Motzer, R.J.; Escudier, B.; McDermott, D.F.; George, S.; Hammers, H.J.; Srinivas, S.; Tykodi, S.S.; Sosman, J.A.; Procopio, G.; Plimack, E.R.; Castellano, D.; Choueiri, T.K.; Gurney, H.; Donskov, F.; Bono, P.; Wagstaff, J.; Gauler, T.C.; Ueda, T.; Tomita, Y.; Schutz, F.A.; Kollmannsberger, C.; Larkin, J.; Ravaud, A.; Simon, J.S.; Xu, L.A.; Waxman, I.M.; Sharma, P. Nivolumab versus everolimus in advanced renal-cell carcinoma. N. Engl. J. Med., 2015, 373(19), 1803-1813.
[http://dx.doi.org/10.1056/NEJMoa1510665] [PMID: 26406148]
[67]
Motzer, R.J.; Tannir, N.M.; McDermott, D.F.; Arén Frontera, O.; Melichar, B.; Choueiri, T.K.; Plimack, E.R.; Barthélémy, P.; Porta, C.; George, S.; Powles, T.; Donskov, F.; Neiman, V.; Kollmannsberger, C.K.; Salman, P.; Gurney, H.; Hawkins, R.; Ravaud, A.; Grimm, M.O.; Bracarda, S.; Barrios, C.H.; Tomita, Y.; Castellano, D.; Rini, B.I.; Chen, A.C.; Mekan, S.; McHenry, M.B.; Wind-Rotolo, M.; Doan, J.; Sharma, P.; Hammers, H.J.; Escudier, B. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N. Engl. J. Med., 2018, 378(14), 1277-1290.
[http://dx.doi.org/10.1056/NEJMoa1712126] [PMID: 29562145]
[68]
Choueiri, T.K.; Larkin, J.; Oya, M.; Thistlethwaite, F.; Martignoni, M.; Nathan, P.; Powles, T.; McDermott, D.; Robbins, P.B.; Chism, D.D.; Cho, D.; Atkins, M.B.; Gordon, M.S.; Gupta, S.; Uemura, H.; Tomita, Y.; Compagnoni, A.; Fowst, C.; di Pietro, A.; Rini, B.I. Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): An open-label, dose-finding and dose-expansion, phase 1b trial. Lancet Oncol., 2018, 19(4), 451-460.
[http://dx.doi.org/10.1016/S1470-2045(18)30107-4] [PMID: 29530667]
[69]
Procopio, G.; Claps, M.; Pircher, C.; Porcu, L.; Sepe, P.; Guadalupi, V.; De Giorgi, U.; Bimbatti, D.; Nolè, F.; Carrozza, F.; Buti, S.; Iacovelli, R.; Ciccarese, C.; Masini, C.; Baldessari, C.; Doni, L.; Cusmai, A.; Gernone, A.; Scagliarini, S.; Pignata, S.; de Braud, F.; Verzoni, E. A multicenter phase 2 single arm study of cabozantinib in patients with advanced or unresectable renal cell carcinoma pre-treated with one immune-checkpoint inhibitor: The BREAKPOINT trial (Meet-Uro trial 03). Tumori, 2023, 109(1), 129-137.
[http://dx.doi.org/10.1177/03008916221138881] [PMID: 36447337]
[70]
Rassy, E.; Flippot, R.; Albiges, L. Tyrosine kinase inhibitors and immunotherapy combinations in renal cell carcinoma. Ther. Adv. Med. Oncol., 2020, 12
[http://dx.doi.org/10.1177/1758835920907504] [PMID: 32215057]
[71]
Sherman, E.; Lee, J.L.; Debruyne, P.R.; Keam, B.; Shin, S.J.; Gramza, A.; Caro, I.; Amin, R.; Shah, K.; Yan, Y.; Huddart, R.; Powles, T. Safety and efficacy of cobimetinib plus atezolizumab in patients with solid tumors: A phase II, open-label, multicenter, multicohort study. ESMO Open, 2023, 8(2), 100877.
[http://dx.doi.org/10.1016/j.esmoop.2023.100877] [PMID: 36947985]
[72]
Braun, D.A.; Bakouny, Z.; Hirsch, L.; Flippot, R.; Van Allen, E.M.; Wu, C.J.; Choueiri, T.K. Beyond conventional immune-checkpoint inhibition — novel immunotherapies for renal cell carcinoma. Nat. Rev. Clin. Oncol., 2021, 18(4), 199-214.
[http://dx.doi.org/10.1038/s41571-020-00455-z] [PMID: 33437048]
[73]
Djajadiningrat, R.S.; Jordanova, E.S.; Kroon, B.K.; van Werkhoven, E.; de Jong, J.; Pronk, D.T.M.; Snijders, P.J.F.; Horenblas, S.; Heideman, D.A.M. Human papillomavirus prevalence in invasive penile cancer and association with clinical outcome. J. Urol., 2015, 193(2), 526-531.
[http://dx.doi.org/10.1016/j.juro.2014.08.087] [PMID: 25150641]
[74]
Ottenhof, S.R.; Djajadiningrat, R.S.; Thygesen, H.H.; Jakobs, P.J.; Jóźwiak, K.; Heeren, A.M.; de Jong, J.; Sanders, J.; Horenblas, S.; Jordanova, E.S. The prognostic value of immune factors in the tumor microenvironment of penile squamous cell carcinoma. Front. Immunol., 2018, 9, 1253.
[http://dx.doi.org/10.3389/fimmu.2018.01253] [PMID: 29942303]
[75]
Udager, A.M.; Liu, T.Y.; Skala, S.L.; Magers, M.J.; McDaniel, A.S.; Spratt, D.E.; Feng, F.Y.; Siddiqui, J.; Cao, X.; Fields, K.L.; Morgan, T.M.; Palapattu, G.S.; Weizer, A.Z.; Chinnaiyan, A.M.; Alva, A.; Montgomery, J.S.; Tomlins, S.A.; Jiang, H.; Mehra, R. Frequent PD-L1 expression in primary and metastatic penile squamous cell carcinoma: Potential opportunities for immunotherapeutic approaches. Ann. Oncol., 2016, 27(9), 1706-1712.
[http://dx.doi.org/10.1093/annonc/mdw216] [PMID: 27217541]
[76]
Davidsson, S.; Carlsson, J.; Giunchi, F.; Harlow, A.; Kirrander, P.; Rider, J.; Fiorentino, M.; Andrén, O. PD-L1 expression in men with penile cancer and its association with clinical outcomes. Eur. Urol. Oncol., 2019, 2(2), 214-221.
[http://dx.doi.org/10.1016/j.euo.2018.07.010] [PMID: 31017099]
[77]
Du, Y.; Zhang, X.; Zhang, Y.; Li, W.; Hu, W.; Zong, L.; Zhao, J. PD-1 inhibitor treatment in a penile cancer patient with MMR/MSI status heterogeneity: A case report. Hum. Vaccin. Immunother., 2022, 18(6), 2121122.
[http://dx.doi.org/10.1080/21645515.2022.2121122] [PMID: 36162043]
[78]
Yan, R.; Ma, H.; Jiang, L.; Guo, S.; Shi, Y.; Sheng, X.; Zhang, Y.; Spiess, P.E.; Liu, T.; Xue, T.; Chen, X.; Li, Z.; An, X.; Yao, K.; Zhou, F.; Han, H. First-line programmed death receptor-1 ( PD -1) inhibitor and epidermal growth factor receptor (EGFR) blockade, combined with platinum-based chemotherapy, for stage IV penile cancer. BJU Int., 2023, 131(2), 198-207.
[http://dx.doi.org/10.1111/bju.15828] [PMID: 35704436]
[79]
Gambale, E.; Fancelli, S.; Caliman, E.; Petrella, M.C.; Doni, L.; Pillozzi, S.; Antonuzzo, L. Immune checkpoint blockade with anti-programmed cell death 1 (PD-1) monoclonal antibody (mAb) cemiplimab: ongoing and future perspectives in rare genital cancers treatment. J. Immunother. Cancer, 2022, 10(1), e003540.
[http://dx.doi.org/10.1136/jitc-2021-003540] [PMID: 35101944]
[80]
Wenzel, M.; Deuker, M.; Nocera, L.; Collà Ruvolo, C.; Tian, Z.; Shariat, S.F.; Saad, F.; Briganti, A.; Becker, A.; Kluth, L.A.; Chun, F.K.H.; Karakiewicz, P.I. Comparison between urothelial and non-urothelial urethral cancer. Front. Oncol., 2021, 10, 629692.
[http://dx.doi.org/10.3389/fonc.2020.629692] [PMID: 33585257]
[81]
Farrell, M.R.; Xu, J.T.; Vanni, A.J. Current perspectives on the diagnosis and management of primary urethral cancer: A systematic review. Res. Rep. Urol., 2021, 13, 325-334.
[http://dx.doi.org/10.2147/RRU.S264720] [PMID: 34104638]
[82]
Flaig, T.W.; Spiess, P.E.; Agarwal, N.; Bangs, R.; Boorjian, S.A.; Buyyounouski, M.K.; Chang, S.; Downs, T.M.; Efstathiou, J.A.; Friedlander, T.; Greenberg, R.E.; Guru, K.A.; Guzzo, T.; Herr, H.W.; Hoffman-Censits, J.; Hoimes, C.; Inman, B.A.; Jimbo, M.; Kader, A.K.; Lele, S.M.; Michalski, J.; Montgomery, J.S.; Nandagopal, L.; Pagliaro, L.C.; Pal, S.K.; Patterson, A.; Plimack, E.R.; Pohar, K.S.; Preston, M.A.; Sexton, W.J.; Siefker-Radtke, A.O.; Tward, J.; Wright, J.L.; Gurski, L.A.; Johnson-Chilla, A. Bladder cancer, version 3.2020, NCCN clinical practice guidelines in oncology. J. Natl. Compr. Canc. Netw., 2020, 18(3), 329-354.
[http://dx.doi.org/10.6004/jnccn.2020.0011] [PMID: 32135513]
[83]
DiMarco, D.S.; DiMarco, C.S.; Zincke, H.; Webb, M.J.; Bass, S.E.; Slezak, J.M.; Lightner, D.J. Surgical treatment for local control of female urethral carcinoma. Urol. Oncol., 2004, 22(5), 404-409.
[http://dx.doi.org/10.1016/S1078-1439(03)00174-1] [PMID: 15464921]
[84]
Mano, R.; Vertosick, E.A.; Sarcona, J.; Sjoberg, D.D.; Benfante, N.E.; Donahue, T.F.; Herr, H.W.; Donat, S.M.; Bochner, B.H.; Dalbagni, G.; Goh, A.C. Primary urethral cancer: Treatment patterns and associated outcomes. BJU Int., 2020, 126(3), 359-366.
[http://dx.doi.org/10.1111/bju.15095] [PMID: 32336001]
[85]
Peyton, C.C.; Azizi, M.; Chipollini, J.; Ercole, C.; Fishman, M.; Gilbert, S.M.; Juwono, T.; Lockhart, J.; Poch, M.; Pow-Sang, J.M.; Spiess, P.E.; Wiegand, L.; Sexton, W.J. Survival outcomes associated with female primary urethral carcinoma: Review of a single institutional experience. Clin. Genitourin. Cancer, 2018, 16(5), e1003-e1013.
[http://dx.doi.org/10.1016/j.clgc.2018.05.012] [PMID: 29859736]
[86]
Lee, W.; Yu, J.; Lee, J.L.; Kim, Y.S.; Hong, B. Clinical features and oncological outcomes of primary female urethral cancer. J. Surg. Oncol., 2022, 125(5), 907-915.
[http://dx.doi.org/10.1002/jso.26790] [PMID: 35050502]
[87]
Zheng, Y.; Xue, Y.Y.; Zhao, Y.Q.; Chen, Y.; Li, Z.P. Disitamab vedotin plus anti-PD-1 antibody show good efficacy in refractory primary urethral cancer with low HER2 expression: A case report. Front. Immunol., 2023, 14, 1254812.
[http://dx.doi.org/10.3389/fimmu.2023.1254812] [PMID: 37901233]
[88]
Bai, H.; Han, H.; Wang, F.; Shi, H. Chemotherapy combined with immunotherapy in primary female urethral squamous cell carcinoma: A case report. J. Int. Med. Res., 2022, 50(10)
[http://dx.doi.org/10.1177/03000605221132418] [PMID: 36281031]
[89]
Ma, J.; Liang, X.; Miao, J.; Li, J.; Wang, X. Immune checkpoint inhibitor in a case with primary urethral adenocarcinoma with lung metastasis. Anticancer Drugs, 2022, 33(10), 1163-1166.
[http://dx.doi.org/10.1097/CAD.0000000000001351] [PMID: 35946533]
[90]
Chen, M.; Yao, K.; Cao, M.; Liu, H.; Xue, C.; Qin, T.; Meng, L.; Zheng, Z.; Qin, Z.; Zhou, F.; Liu, Z.; Shi, Y.; An, X. HER2-targeting antibody–drug conjugate RC48 alone or in combination with immunotherapy for locally advanced or metastatic urothelial carcinoma: A multicenter, real-world study. Cancer Immunol. Immunother., 2023, 72(7), 2309-2318.
[http://dx.doi.org/10.1007/s00262-023-03419-1] [PMID: 36897337]
[91]
Rosenberg, J.E.; Hoffman-Censits, J.; Powles, T.; van der Heijden, M.S.; Balar, A.V.; Necchi, A.; Dawson, N.; O’Donnell, P.H.; Balmanoukian, A.; Loriot, Y.; Srinivas, S.; Retz, M.M.; Grivas, P.; Joseph, R.W.; Galsky, M.D.; Fleming, M.T.; Petrylak, D.P.; Perez-Gracia, J.L.; Burris, H.A.; Castellano, D.; Canil, C.; Bellmunt, J.; Bajorin, D.; Nickles, D.; Bourgon, R.; Frampton, G.M.; Cui, N.; Mariathasan, S.; Abidoye, O.; Fine, G.D.; Dreicer, R. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial. Lancet, 2016, 387(10031), 1909-1920.
[http://dx.doi.org/10.1016/S0140-6736(16)00561-4] [PMID: 26952546]
[92]
Belfield, J.; Findlay-Line, C. Testicular germ cell tumours—the role of conventional ultrasound. Cancers, 2022, 14(16), 3882.
[http://dx.doi.org/10.3390/cancers14163882] [PMID: 36010875]
[93]
Cierna, Z.; Mego, M.; Miskovska, V.; Machalekova, K.; Chovanec, M.; Svetlovska, D.; Hainova, K.; Rejlekova, K.; Macak, D.; Spanik, S.; Ondrus, D.; Kajo, K.; Mardiak, J.; Babal, P. Prognostic value of programmed-death-1 receptor (PD-1) and its ligand 1 (PD-L1) in testicular germ cell tumors. Ann. Oncol., 2016, 27(2), 300-305.
[http://dx.doi.org/10.1093/annonc/mdv574] [PMID: 26598537]
[94]
Cheng, X.; Dai, H.; Wan, N.; Moore, Y.; Vankayalapati, R.; Dai, Z. Interaction of programmed death-1 and programmed death-1 ligand-1 contributes to testicular immune privilege. Transplantation, 2009, 87(12), 1778-1786.
[http://dx.doi.org/10.1097/TP.0b013e3181a75633] [PMID: 19543053]
[95]
Jennewein, L.; Bartsch, G.; Gust, K.; Kvasnicka, H.M.; Haferkamp, A.; Blaheta, R.; Mittelbronn, M.; Harter, P.; Mani, J. Increased tumor vascularization is associated with the amount of immune competent PD‑1 positive cells in testicular germ cell tumors. Oncol. Lett., 2018, 15(6), 9852-9860.
[http://dx.doi.org/10.3892/ol.2018.8597] [PMID: 29928359]
[96]
Fankhauser, C.D.; Curioni-Fontecedro, A.; Allmann, V.; Beyer, J.; Tischler, V.; Sulser, T.; Moch, H.; Bode, P.K. Frequent PD-L1 expression in testicular germ cell tumors. Br. J. Cancer, 2015, 113(3), 411-413.
[http://dx.doi.org/10.1038/bjc.2015.244] [PMID: 26171934]
[97]
Chovanec, M.; Cierna, Z.; Miskovska, V.; Machalekova, K.; Svetlovska, D.; Kalavska, K.; Rejlekova, K.; Spanik, S.; Kajo, K.; Babal, P.; Mardiak, J.; Mego, M. Prognostic role of programmed-death ligand 1 (PD-L1) expressing tumor infiltrating lymphocytes in testicular germ cell tumors. Oncotarget, 2017, 8(13), 21794-21805.
[http://dx.doi.org/10.18632/oncotarget.15585] [PMID: 28423520]
[98]
Tu, Z.; Peng, J.; Long, X.; Li, J.; Wu, L.; Huang, K.; Zhu, X. Sperm autoantigenic protein 17 predicts the prognosis and the immunotherapy response of cancers: A pan-cancer analysis. Front. Immunol., 2022, 13, 844736.
[http://dx.doi.org/10.3389/fimmu.2022.844736] [PMID: 35592314]
[99]
Ratta, R.; Zappasodi, R.; Raggi, D.; Grassi, P.; Verzoni, E.; Necchi, A.; Di Nicola, M.; Salvioni, R.; de Braud, F.; Procopio, G. Immunotherapy advances in uro-genital malignancies. Crit. Rev. Oncol. Hematol., 2016, 105, 52-64.
[http://dx.doi.org/10.1016/j.critrevonc.2016.06.012] [PMID: 27372200]
[100]
Semaan, A.; Haddad, F.G.H.; Eid, R.; Kourie, H.R.; Nemr, E. Immunotherapy: Last bullet in platinum refractory germ cell testicular cancer. Future Oncol., 2019, 15(5), 533-541.
[http://dx.doi.org/10.2217/fon-2018-0571] [PMID: 30624089]
[101]
Shah, S.; Ward, J.E.; Bao, R.; Hall, C.R.; Brockstein, B.E.; Luke, J.J. Clinical response of a patient to anti–PD-1 immunotherapy and the immune landscape of testicular germ cell tumors. Cancer Immunol. Res., 2016, 4(11), 903-909.
[http://dx.doi.org/10.1158/2326-6066.CIR-16-0087] [PMID: 27638840]

© 2025 Bentham Science Publishers | Privacy Policy