Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–249.
Google ScholarÂ
Vlachostergios PJ, Faltas BM. Treatment resistance in urothelial carcinoma: an evolutionary perspective. Nat Rev Clin Oncol. 2018;15:495–509.
Google ScholarÂ
Champiat S, Dercle L, Ammari S, Massard C, Hollebecque A, Postel-Vinay S, et al. Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. Clin Cancer Res. 2017;23:1920–8.
Google ScholarÂ
Lopez-Beltran A, Cookson MS, Guercio BJ, Cheng L. Advances in diagnosis and treatment of bladder cancer. BMJ (Clin Res ed). 2024;384:e076743.
Felsenstein KM, Theodorescu D. Precision medicine for urothelial bladder cancer: update on tumour genomics and immunotherapy. Nat Rev Urol. 2018;15:92–111.
Google ScholarÂ
Meeks JJ, Al-Ahmadie H, Faltas BM, Taylor JA 3rd, Flaig TW, et al. Genomic heterogeneity in bladder cancer: challenges and possible solutions to improve outcomes. Nat Rev Urol. 2020;17:259–70.
Google ScholarÂ
Schneider AK, Chevalier MF, Derré L. The multifaceted immune regulation of bladder cancer. Nat Rev Urol. 2019;16:613–30.
Google ScholarÂ
Hassin O, Oren M. Drugging p53 in cancer: one protein, many targets. Nat Rev Drug Discov. 2023;22:127–44.
Google ScholarÂ
Jin K, Xu J, Su X, Xu Z, Li B, Liu G, et al. TP53 disruptive mutation predicts platinum-based chemotherapy and PD-1/PD-L1 blockade response in urothelial carcinoma. J Pathol. 2024;263:139–49.
Google ScholarÂ
Choi W, Porten S, Kim S, Willis D, Plimack ER, Hoffman-Censits J, et al. Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell. 2014;25:152–65.
Google ScholarÂ
Blagih J, Zani F, Chakravarty P, Hennequart M, Pilley S, Hobor S, et al. Cancer-Specific Loss of p53 Leads to a Modulation of Myeloid and T Cell Responses. Cell Rep. 2020;30:481–96.e486.
Google ScholarÂ
van Weverwijk A, de Visser KE. Mechanisms driving the immunoregulatory function of cancer cells. Nat Rev Cancer. 2023;23:193–215.
Google ScholarÂ
Wellenstein MD, Coffelt SB, Duits DEM, van Miltenburg MH, Slagter M, de Rink I, et al. Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis. Nature. 2019;572:538–42.
Google ScholarÂ
Maddalena M, Mallel G, Nataraj NB, Shreberk-Shaked M, Hassin O, Mukherjee S, et al. TP53 missense mutations in PDAC are associated with enhanced fibrosis and an immunosuppressive microenvironment. Proc Natl Acad Sci USA. 2021;118:e2025631118.
Robertson AG, Kim J, Al-Ahmadie H, Bellmunt J, Guo G, Cherniack AD, et al. Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell. 2018;174:1033.
Google ScholarÂ
Damrauer JS, Beckabir W, Klomp J, Zhou M, Plimack ER, Galsky MD, et al. Collaborative study from the Bladder Cancer Advocacy Network for the genomic analysis of metastatic urothelial cancer. Nat Commun. 2022;13:6658.
Google ScholarÂ
Mariathasan S, Turley SJ, Nickles D, Castiglioni A, Yuen K, Wang Y, et al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018;554:544–8.
Google ScholarÂ
Oaknin A, Bosse TJ, Creutzberg CL, Giornelli G, Harter P, Joly F, et al. Endometrial cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33:860–77.
Google ScholarÂ
Singh N, Piskorz AM, Bosse T, Jimenez-Linan M, Rous B, Brenton JD, et al. p53 immunohistochemistry is an accurate surrogate for TP53 mutational analysis in endometrial carcinoma biopsies. J Pathol. 2020;250:336–45.
Google ScholarÂ
Fu Q, Xu L, Wang Y, Jiang Q, Liu Z, Zhang J, et al. Tumor-associated Macrophage-derived Interleukin-23 Interlinks Kidney Cancer Glutamine Addiction with Immune Evasion. Eur Urol. 2019;75:752–63.
Google ScholarÂ
van der Leun AM, Thommen DS, Schumacher TN. CD8(+) T cell states in human cancer: insights from single-cell analysis. Nat Rev Cancer. 2020;20:218–32.
Google ScholarÂ
Oliveira G, Stromhaug K, Klaeger S, Kula T, Frederick DT, Le PM, et al. Phenotype, specificity and avidity of antitumour CD8(+) T cells in melanoma. Nature. 2021;596:119–25.
Google ScholarÂ
Lowery FJ, Krishna S, Yossef R, Parikh NB, Chatani PD, Zacharakis N, et al. Molecular signatures of antitumor neoantigen-reactive T cells from metastatic human cancers. Science. 2022;375:877–84.
Google ScholarÂ
Meng Z, Rodriguez Ehrenfried A, Tan CL, Steffens LK, Kehm H, Zens S, et al. Transcriptome-based identification of tumor-reactive and bystander CD8(+) T cell receptor clonotypes in human pancreatic cancer. Sci Transl Med. 2023;15:eadh9562.
Google ScholarÂ
Tran MA, Cho BA, Izadmehr S, Yoo SK, Youssef D, Anker JF et al. A tumor-promoting inflammatory SPP1+ macrophage-IL-6-CRP axis drives immune dysfunction in bladder cancer. Cancer Discov https://doi.org/10.1158/2159-8290.Cd-25-1774 (2026).
Efe G, Rustgi AK, Prives C. p53 at the crossroads of tumor immunity. Nat Cancer. 2024;5:983–95.
Google ScholarÂ
Bruni D, Angell HK, Galon J. The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy. Nat Rev Cancer. 2020;20:662–80.
Google ScholarÂ
Lee YC, Lam HM, Rosser C, Theodorescu D, Parks WC, Chan KS. The dynamic roles of the bladder tumour microenvironment. Nat Rev Urol. 2022;19:515–33.
Google ScholarÂ
Vidotto T, Nersesian S, Graham C, Siemens DR, Koti M. DNA damage repair gene mutations and their association with tumor immune regulatory gene expression in muscle invasive bladder cancer subtypes. J Immunother cancer. 2019;7:148.
Google ScholarÂ
Kobatake K, Ikeda KI, Nakata Y, Yamasaki N, Ueda T, Kanai A, et al. Kdm6a Deficiency Activates Inflammatory Pathways, Promotes M2 Macrophage Polarization, and Causes Bladder Cancer in Cooperation with p53 Dysfunction. Clin Cancer Res: Off J Am Assoc Cancer Res. 2020;26:2065–79.
Google ScholarÂ
Song Y, Peng Y, Qin C, Wang Y, Yang W, Du Y, et al. Fibroblast growth factor receptor 3 mutation attenuates response to immune checkpoint blockade in metastatic urothelial carcinoma by driving immunosuppressive microenvironment. J Immunother Cancer. 2023;11:e006643.
Levine AJ. p53: 800 million years of evolution and 40 years of discovery. Nat Rev Cancer. 2020;20:471–80.
Google ScholarÂ
Togashi Y, Shitara K, Nishikawa H. Regulatory T cells in cancer immunosuppression – implications for anticancer therapy. Nat Rev Clin Oncol. 2019;16:356–71.
Google ScholarÂ
Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood. 2007;109:3812–9.
Google ScholarÂ
Hanahan D, Michielin O, Pittet MJ. Convergent inducers and effectors of T cell paralysis in the tumour microenvironment. Nat Rev Cancer. 2025;25:41–58.
Google ScholarÂ
Anderson KG, Stromnes IM, Greenberg PD. Obstacles posed by the tumor microenvironment to T cell activity: a case for synergistic therapies. Cancer cell. 2017;31:311–25.
Google ScholarÂ

