Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. Cancer J Clin. 2021;71(3):209–49.

Article  Google Scholar 

Lotan Y, Kamat AM, Porter MP, Robinson VL, Shore N, Jewett M, Schelhammer PF, White R, Quale D, Lee CT. Key concerns about the current state of Bladder cancer. Cancer. 2009;115(18):4096–103.

Article  PubMed  Google Scholar 

Patel VG, Oh WK, Galsky MD. Treatment of muscle-invasive and advanced Bladder cancer in 2020. Cancer J Clin. 2020;70(5):404–23.

Article  Google Scholar 

Chang SS, Bochner BH, Chou R, Dreicer R, Kamat AM, Lerner SP, Lotan Y, Meeks JJ, Michalski JM, Morgan TM, et al. Treatment of non-metastatic muscle-invasive Bladder Cancer: AUA/ASCO/ASTRO/SUO Guideline. J Urol. 2017;198(3):552–9.

Article  PubMed  PubMed Central  Google Scholar 

Stenehjem D, Tran D, Nkrumah M, Gupta S. PD1/PDL1 inhibitors for the treatment of advanced urothelial Bladder cancer. OncoTargets and Therapy. 2018;11:5973–89.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Lenis AT, Lec PM, Chamie K, Mshs MD. Bladder Cancer. Jama 2020, 324(19).

Carril-Ajuria L, Martin-Soberón MC, de Velasco G, Agarwal N, Castellano D. Immunotherapy maintenance therapy for advanced urothelial carcinoma (aUC): a comprehensive review. J Cancer Res Clin Oncol. 2022;148(5):1097–105.

Article  PubMed  Google Scholar 

Patwardhan MV, Mahendran R. The bladder Tumor Microenvironment Components that modulate the Tumor and Impact Therapy. Int J Mol Sci 2023, 24(15).

Biffi G, Tuveson DA. Diversity and Biology of Cancer-Associated fibroblasts. Physiol Rev. 2021;101(1):147–76.

Article  PubMed  CAS  Google Scholar 

Chen X, Song E. Turning foes to friends: targeting cancer-associated fibroblasts. Nat Rev Drug Discovery. 2018;18(2):99–115.

Article  Google Scholar 

Lee JW, Liu L, Liu L, Yao HH, Zhu ZQ, Ning ZL, Huang Q. Stromal Myofibroblasts Are Associated with Poor Prognosis in Solid Cancers: A Meta-Analysis of Published Studies. Plos One 2016, 11(7).

Zhang Z, Liang Z, Li D, Wang L, Chen Y, Liang Y, Jiao W, Niu H. Development of a CAFs-related gene signature to predict survival and drug response in Bladder cancer. Hum Cell. 2022;35(2):649–64.

Article  PubMed  CAS  Google Scholar 

Mhaidly R, Mechta-Grigoriou F. Fibroblast heterogeneity in Tumor micro-environment: role in immunosuppression and new therapies. Semin Immunol 2020, 48.

Racle J, de Jonge K, Baumgaertner P, Speiser DE, Gfeller D. Simultaneous enumeration of cancer and immune cell types from bulk Tumor gene expression data. eLife 2017, 6.

Aran D, Hu Z, Butte AJ. xCell: digitally portraying the tissue cellular heterogeneity landscape. Genome Biol 2017, 18(1).

Becht E, Giraldo NA, Lacroix L, Buttard B, Elarouci N, Petitprez F, Selves J, Laurent-Puig P, Sautès-Fridman C, Fridman WH et al. Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression. Genome Biol 2016, 17(1).

Kamoun A, de Reyniès A, Allory Y, Sjödahl G, Robertson AG, Seiler R, Hoadley KA, Groeneveld CS, Al-Ahmadie H, Choi W, et al. A Consensus Molecular classification of muscle-invasive Bladder Cancer. Eur Urol. 2020;77(4):420–33.

Article  PubMed  Google Scholar 

Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z, Feng T, Zhou L, Tang W, Zhan L et al. clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. The Innovation 2021, 2(3).

Hänzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics. 2013;14:7.

Article  PubMed  PubMed Central  Google Scholar 

Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, Hoang CD, Diehn M, Alizadeh AA. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12(5):453–7.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Chen Z, Zhou L, Liu L, Hou Y, Xiong M, Yang Y, Hu J, Chen K. Single-cell RNA sequencing highlights the role of inflammatory cancer-associated fibroblasts in bladder urothelial carcinoma. Nat Commun 2020, 11(1).

Butler A, Hoffman P, Smibert P, Papalexi E, Satija R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 2018;36(5):411–20.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Vivacqua A, Muoio M, Miglietta A, Maggiolini M. Differential MicroRNA Landscape triggered by Estrogens in Cancer Associated fibroblasts (CAFs) of primary and metastatic breast tumors. Cancers 2019, 11(3).

Yu Y, Liang Y, Li D, Wang L, Liang Z, Chen Y, Ma G, Wu H, Jiao W, Niu H. Glucose metabolism involved in PD-L1-mediated immune Escape in the malignant kidney tumour microenvironment. Cell Death Discovery 2021, 7(1).

Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9(7):671–5.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Nurmik M, Ullmann P, Rodriguez F, Haan S, Letellier E. In search of definitions: Cancer-associated fibroblasts and their markers. Int J Cancer. 2019;146(4):895–905.

Article  PubMed  PubMed Central  Google Scholar 

Chen Y, McAndrews KM, Kalluri R. Clinical and therapeutic relevance of cancer-associated fibroblasts. Nat Reviews Clin Oncol. 2021;18(12):792–804.

Article  CAS  Google Scholar 

Ning S, Wang L. The multifunctional protein p62 and its mechanistic roles in cancers. Curr Cancer Drug Targets. 2019;19(6):468–78.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Lane JD, Korolchuk VI, Murray JT, Lamark T, Svenning S, Johansen T. Regulation of selective autophagy: the p62/SQSTM1 paradigm. Essays Biochem. 2017;61(6):609–24.

Article  Google Scholar 

Farshi P, Deshmukh RR, Nwankwo JO, Arkwright RT, Cvek B, Liu J, Dou QP. Deubiquitinases (DUBs) and DUB inhibitors: a patent review. Expert Opin Ther Pat. 2015;25(10):1191–208.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ha J, Kim M, Seo D, Park JS, Lee J, Lee J, Park SH. The deubiquitinating enzyme USP20 regulates the TNFα-Induced NF-κB signaling pathway through stabilization of p62. Int J Mol Sci 2020, 21(9).

Nibe Y, Oshima S, Kobayashi M, Maeyashiki C, Matsuzawa Y, Otsubo K, Matsuda H, Aonuma E, Nemoto Y, Nagaishi T et al. Novel polyubiquitin imaging system, PolyUb-FC, reveals that K33-linked polyubiquitin is recruited by SQSTM1/p62. Autophagy 2018, 14(2):347–358.

Peng H, Yang F, Hu Q, Sun J, Peng C, Zhao Y, Huang C. The ubiquitin-specific protease USP8 directly deubiquitinates SQSTM1/p62 to suppress its autophagic activity. Autophagy. 2019;16(4):698–708.

Article  PubMed  PubMed Central  Google Scholar 

Lyu L, Lin T-C, McCarty N. TRIM44 mediated p62 deubiquitination enhances DNA damage repair by increasing nuclear FLNA and 53BP1 expression. Oncogene. 2021;40(32):5116–30.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Xie W, Tian S, Yang J, Cai S, Jin S, Zhou T, Wu Y, Chen Z, Ji Y, Cui J. OTUD7B deubiquitinates SQSTM1/p62 and promotes IRF3 degradation to regulate antiviral immunity. Autophagy. 2022;18(10):2288–302.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Mortezaee K. CXCL12/CXCR4 axis in the microenvironment of solid tumors: a critical mediator of Metastasis. Life Sci 2020, 249.

Chen Y, Liu Y, Wang Y, Chen X, Wang C, Chen X, Yuan X, Liu L, Yang J, Zhou X. Prevotellaceae produces butyrate to alleviate PD-1/PD-L1 inhibitor-related cardiotoxicity via PPARα-CYP4X1 axis in colonic macrophages. J Experimental Clin Cancer Res 2022, 41(1).

Xu H-Z, Li T-F, Wang C, Ma Y, Liu Y, Zheng M-Y, Liu Z-J-Y, Chen J-B, Li K, Sun S-K et al. Synergy of nanodiamond–doxorubicin conjugates and PD-L1 blockade effectively turns tumor-associated macrophages against Tumor cells. J Nanobiotechnol 2021, 19(1).

Caramelo B, Zagorac S, Corral S, Marqués M, Real FX. Cancer-associated fibroblasts in Bladder Cancer: Origin, Biology, and Therapeutic opportunities. Eur Urol Oncol. 2023;6(4):366–75.

Article  PubMed  Google Scholar 

Luo H, Xia X, Huang L-B, An H, Cao M, Kim GD, Chen H-N, Zhang W-H, Shu Y, Kong X et al. Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the Tumor microenvironment. Nat Commun 2022, 13(1).

Mao X, Xu J, Wang W, Liang C, Hua J, Liu J, Zhang B, Meng Q, Yu X, Shi S. Crosstalk between cancer-associated fibroblasts and immune cells in the Tumor microenvironment: new findings and future perspectives. Mol Cancer 2021, 20(1).

Wang Y, Lan W, Xu M, Song J, Mao J, Li C, Du X, Jiang Y, Li E, Zhang R et al. Cancer-associated fibroblast-derived SDF-1 induces epithelial-mesenchymal transition of lung adenocarcinoma via CXCR4/β-catenin/PPARδ signalling. Cell Death Dis 2021, 12(2).

Wei L, Ye H, Li G, Lu Y, Zhou Q, Zheng S, Lin Q, Liu Y, Li Z, Chen R. Cancer-associated fibroblasts promote progression and gemcitabine resistance via the SDF-1/SATB-1 pathway in Pancreatic cancer. Cell Death Dis 2018, 9(11).

Nazari A, Khorramdelazad H, Hassanshahi G. Biological/pathological functions of the CXCL12/CXCR4/CXCR7 axes in the pathogenesis of Bladder cancer. Int J Clin Oncol. 2017;22(6):991–1000.

Article  PubMed  CAS  Google Scholar 

Teicher BA, Fricker SP. CXCL12 (SDF-1)/CXCR4 pathway in Cancer. Clin Cancer Res. 2010;16(11):2927–31.

Article  PubMed  CAS  Google Scholar 

Lv J, Zhu Y, Ji A, Zhang Q, Liao G. Mining TCGA database for Tumor mutation burden and their clinical significance in Bladder cancer. Biosci Rep 2020, 40(4).

Wang J, Xie Y, Qin D, Zhong S, Hu X. CXCL12, a potential modulator of Tumor immune microenvironment (TIME) of Bladder cancer: from a comprehensive analysis of TCGA database. Front Oncol 2022, 12.

Chaudary N, Hill RP, Stulik L, Milosevic M. The oral CXCR4 inhibitor X4-136 improves Tumor Control and reduces toxicity in Cervical Cancer treated with Radiation Therapy and Concurrent Chemotherapy. Int J Radiation Oncology*Biology*Physics. 2021;110(5):1317–24.

Article  Google Scholar 

D’Alterio C, Buoncervello M, Ieranò C, Napolitano M, Portella L, Rea G, Barbieri A, Luciano A, Scognamiglio G, Tatangelo F et al. Targeting CXCR4 potentiates anti-PD-1 efficacy modifying the Tumor microenvironment and inhibiting neoplastic PD-1. J Experimental Clin Cancer Res 2019, 38(1).

Wang X, Wu WKK, Gao J, Li Z, Dong B, Lin X, Li Y, Li Y, Gong J, Qi C et al. Autophagy inhibition enhances PD-L1 expression in gastric cancer. J Experimental Clin Cancer Res 2019, 38(1).

Wang H, Yao H, Li C, Shi H, Lan J, Li Z, Zhang Y, Liang L, Fang J-Y, Xu J. HIP1R targets PD-L1 to lysosomal degradation to alter T cell–mediated cytotoxicity. Nat Chem Biol. 2018;15(1):42–50.

Article  PubMed  Google Scholar 

Li T, Jiang D, Wu K. p62 promotes Bladder cancer cell growth by activating KEAP1/NRF2-dependent antioxidative response. Cancer Sci. 2020;111(4):1156–64.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Li H, Kuang X, Liang L, Ye Y, Zhang Y, Li J, Ma F, Tao J, Lei G, Zhao S et al. The beneficial role of Sunitinib in Tumor Immune Surveillance by regulating Tumor PD-L1. Adv Sci 2020, 8(2).

Zhang D, Man D, Lu J, Jiang Y, Ding B, Su R, Tong R, Chen J, Yang B, Zheng S et al. Mitochondrial TSPO promotes Hepatocellular Carcinoma Progression through Ferroptosis Inhibition and Immune Evasion. Adv Sci 2023, 10(15).

Ene–Obong A, Clear AJ, Watt J, Wang J, Fatah R, Riches JC, Marshall JF, Chin–Aleong J, Chelala C, Gribben JG, et al. Activated pancreatic stellate cells sequester CD8 + T cells to reduce their infiltration of the Juxtatumoral compartment of pancreatic ductal adenocarcinoma. Gastroenterology. 2013;145(5):1121–32.

Article  PubMed  Google Scholar 

Feig C, Jones JO, Kraman M, Wells RJB, Deonarine A, Chan DS, Connell CM, Roberts EW, Zhao Q, Caballero OL et al. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti–PD-L1 immunotherapy in pancreatic cancer. Proceedings of the National Academy of Sciences 2013, 110(50):20212–20217.