101
Views
0
CrossRef citations to date
0
Altmetric
Review

Established and Emerging Biomarkers of Immunotherapy in Renal Cell Carcinoma

ORCID Icon, ORCID Icon, ORCID Icon &
Pages 405-426 | Received 17 Oct 2023, Accepted 08 Jan 2024, Published online: 24 Jan 2024

References

  • Martin SD , BhuiyanI, SoleimaniM, WangG. Biomarkers for immune checkpoint inhibitors in renal cell carcinoma. J. Clin. Med.12(15), 4987 (2023).
  • Chen F , ZhangY, ŞenbabaoğluYet al. Multilevel genomics-based taxonomy of renal cell carcinoma. Cell. Rep.14(10), 2476–2489 (2016).
  • Iacovelli R , SternbergCN, PortaCet al. Inhibition of the VEGF/VEGFR pathway improves survival in advanced kidney cancer: a systematic review and meta-analysis. Curr. Drug Targets16(2), 164–170 (2015).
  • Rini BI , AtkinsMB. Resistance to targeted therapy in renal-cell carcinoma. Lancet Oncol.10(10), 992–1000 (2009).
  • Motzer RJ , EscudierB, McdermottDFet al. Nivolumab versus Everolimus in advanced renal-cell carcinoma. N. Engl. J. Med.373(19), 1803–1813 (2015).
  • Motzer RJ , TannirNM, McdermottDFet al. Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma. N. Engl. J. Med.378(14), 1277–1290 (2018).
  • Wong JSL , KwokGGW, TangVet al. Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors. J Immunother Cancer9(2), (2021).
  • Chen J , JiangCC, JinL, ZhangXD. Regulation of PD-L1: a novel role of pro-survival signalling in cancer. Ann. Oncol.27(3), 409–416 (2016).
  • Ai L , XuA, XuJ. Roles of PD-1/PD-L1 pathway: signaling, cancer, and beyond. Adv. Exp. Med. Biol.1248, 33–59 (2020).
  • Maleki Vareki S , GarrigósC, DuranI. Biomarkers of response to PD-1/PD-L1 inhibition. Crit. Rev. Oncol. Hematol.116, 116–124 (2017).
  • Patel SP , KurzrockR. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther14(4), 847–856 (2015).
  • Xu W , AtkinsMB, McdermottDF. Checkpoint inhibitor immunotherapy in kidney cancer. Nat Rev Urol17(3), 137–150 (2020).
  • Paz-Ares L , LuftA, VicenteDet al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N. Engl. J. Med.379(21), 2040–2051 (2018).
  • Robert C , LongGV, BradyBet al. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med.372(4), 320–330 (2015).
  • Choueiri TK , PowlesT, BurottoMet al. Nivolumab plus Cabozantinib versus Sunitinib for advanced renal-cell carcinoma. N. Engl. J. Med.384(9), 829–841 (2021).
  • Samstein RM , LeeCH, ShoushtariANet al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat. Genet.51(2), 202–206 (2019).
  • Guida A , SabbatiniR, GibelliniL, DeBiasi S, CossarizzaA, PortaC. Finding predictive factors for immunotherapy in metastatic renal-cell carcinoma: what are we looking for?Cancer Treat. Rev.94, 102157 (2021).
  • Czyzyk-Krzeska MF , LanderoFigueroa JA, GulatiSet al. Molecular and Metabolic Subtypes in Sporadic and Inherited Clear Cell Renal Cell Carcinoma. Genes (Basel)12(3), 388 (2021).
  • Topalian SL , HodiFS, BrahmerJRet al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N. Engl. J. Med.366(26), 2443–2454 (2012).
  • Paver EC , CooperWA, ColebatchAJet al. Programmed death ligand-1 (PD-L1) as a predictive marker for immunotherapy in solid tumors: a guide to immunohistochemistry implementation and interpretation. Pathology53(2), 141–156 (2021).
  • Khunger M , HernandezAV, PasupuletiVet al. Programmed cell death 1 (PD-1) ligand (PD-L1) expression in solid tumors as a predictive biomarker of benefit from PD-1/PD-L1 axis inhibitors: a systematic review and meta-analysis. JCO Precis Oncol.1, 1–15 (2017).
  • Carretero-González A , LoraD, MartínSobrino Iet al. The value of PD-L1 expression as predictive biomarker in metastatic renal cell carcinoma patients: a meta-analysis of randomized clinical trials. Cancers (Basel)12(7), 1945 (2020).
  • Motzer R , AlekseevB, RhaSYet al. Lenvatinib plus Pembrolizumab or Everolimus for advanced renal cell carcinoma. N. Engl. J. Med.384(14), 1289–1300 (2021).
  • Callea M , AlbigesL, GuptaMet al. Differential expression of PD-L1 between primary and metastatic sites in clear-cell renal cell carcinoma. Cancer Immunol. Res.3(10), 1158–1164 (2015).
  • Motzer RJ , RiniBI, McdermottDFet al. Nivolumab for metastatic renal cell carcinoma: results of a randomized Phase II trial. J. Clin. Oncol.33(13), 1430–1437 (2015).
  • Yearley JH , GibsonC, YuNet al. PD-L2 Expression in Human Tumors: Relevance to Anti-PD-1 Therapy in Cancer. Clin. Cancer Res.23(12), 3158–3167 (2017).
  • Rini BI , PowlesT, AtkinsMBet al. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet393(10189), 2404–2415 (2019).
  • Yarchoan M , HopkinsA, JaffeeEM. Tumor Mutational Burden and Response Rate to PD-1 Inhibition. N. Engl. J. Med.377(25), 2500–2501 (2017).
  • Motzer RJ , RobbinsPB, PowlesTet al. Avelumab plus axitinib versus sunitinib in advanced renal cell carcinoma: biomarker analysis of the phase 3 JAVELIN Renal 101 trial. Nat. Med.26(11), 1733–1741 (2020).
  • Marchetti A , RoselliniM, MollicaVet al. The Molecular Characteristics of Non-Clear Cell Renal Cell Carcinoma: What’s the Story Morning Glory? Int. J. Mol. Sci. 22(12), 6237 (2021).
  • Pichler R , CompératE, KlatteTet al. Renal Cell Carcinoma with Sarcomatoid Features: Finally New Therapeutic Hope? Cancers (Basel) 11(3), (2019).
  • Motzer RJ , RiniBI, McdermottDFet al. Nivolumab plus ipilimumab versus sunitinib in first-line treatment for advanced renal cell carcinoma: extended follow-up of efficacy and safety results from a randomised, controlled, phase 3 trial. Lancet Oncol.20(10), 1370–1385 (2019).
  • Powles T , PlimackER, SoulièresDet al. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. Lancet Oncol.21(12), 1563–1573 (2020).
  • Tannir NM , SignorettiS, ChoueiriTKet al. Efficacy and Safety of Nivolumab Plus Ipilimumab versus Sunitinib in First-line Treatment of Patients with Advanced Sarcomatoid Renal Cell Carcinoma. Clin. Cancer Res.27(1), 78–86 (2021).
  • D’costa NM , CinaD, ShresthaRet al. Identification of gene signature for treatment response to guide precision oncology in clear-cell renal cell carcinoma. Sci. Rep.10(1), 2026 (2020).
  • Yoshida T , OheC, IkedaJet al. Eosinophilic features in clear cell renal cell carcinoma correlate with outcomes of immune checkpoint and angiogenesis blockade. J. Immunother. Cancer9(9), e002922 (2021).
  • Gulati S , VogelzangNJ. Biomarkers in renal cell carcinoma: are we there yet?Asian J. Urol.8(4), 362–375 (2021).
  • Mano R , DuzgolC, GanatMet al. Somatic mutations as preoperative predictors of metastases in patients with localized clear cell renal cell carcinoma - an exploratory analysis. Urol. Oncol.39(11), 791.e717–791.e724 (2021).
  • Varela I , TarpeyP, RaineKet al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature469(7331), 539–542 (2011).
  • Miao D , MargolisCA, GaoWet al. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science359(6377), 801–806 (2018).
  • Braun DA , IshiiY, WalshAMet al. Clinical Validation of PBRM1 Alterations as a Marker of Immune Checkpoint Inhibitor Response in Renal Cell Carcinoma. JAMA Oncol.5(11), 1631–1633 (2019).
  • Dai J , CuiY, LiangXet al. PBRM1 mutation as a predictive biomarker for immunotherapy in multiple cancers. Front. Genet.13, 1066347 (2022).
  • Kapur P , Peña-LlopisS, ChristieAet al. Effects on survival of BAP1 and PBRM1 mutations in sporadic clear-cell renal-cell carcinoma: a retrospective analysis with independent validation. Lancet Oncol.14(2), 159–167 (2013).
  • Joseph RW , KapurP, SerieDJet al. Loss of BAP1 protein expression is an independent marker of poor prognosis in patients with low-risk clear cell renal cell carcinoma. Cancer120(7), 1059–1067 (2014).
  • Li F , AljahdaliIaM, ZhangR, NastiukKL, KrolewskiJJ, LingX. Kidney cancer biomarkers and targets for therapeutics: survivin (BIRC5), XIAP, MCL-1, HIF1α, HIF2α, NRF2, MDM2, MDM4, p53, KRAS and AKT in renal cell carcinoma. J. Exp. Clin. Cancer Res.40(1), 254 (2021).
  • Moreira M , PobelC, EpaillardN, SimonaggioA, OudardS, VanoYA. Resistance to cancer immunotherapy in metastatic renal cell carcinoma. Cancer Drug Resist.3(3), 454–471 (2020).
  • Voss MH , ReisingA, ChengYet al. Genomically annotated risk model for advanced renal-cell carcinoma: a retrospective cohort study. Lancet Oncol.19(12), 1688–1698 (2018).
  • Chen R , ZhaoWQ, FangC, YangX, JiM. Histone methyltransferase SETD2: a potential tumor suppressor in solid cancers. J. Cancer11(11), 3349–3356 (2020).
  • Hakimi AA , OstrovnayaI, RevaBet al. Adverse outcomes in clear cell renal cell carcinoma with mutations of 3p21 epigenetic regulators BAP1 and SETD2: a report by MSKCC and the KIRC TCGA research network. Clin. Cancer Res.19(12), 3259–3267 (2013).
  • Zheng X , LinJ, XiongJet al. SETD2 variation correlates with tumor mutational burden and MSI along with improved response to immunotherapy. BMC Cancer23(1), 686 (2023).
  • Liu Y , GouX, WeiZ, YuH, ZhouX, LiX. Bioinformatics profiling integrating a four immune-related long non-coding RNAs signature as a prognostic model for papillary renal cell carcinoma. Aging (Albany NY)12(15), 15359–15373 (2020).
  • Ho TH , ChoueiriTK, WangKet al. Correlation Between Molecular Subclassifications of Clear Cell Renal Cell Carcinoma and Targeted Therapy Response. Eur. Urol. Focus2(2), 204–209 (2016).
  • Hagiwara M , FushimiA, MatsumotoK, OyaM. The Significance of PARP1 as a biomarker for Predicting the Response to PD-L1 Blockade in Patients with PBRM1-mutated Clear Cell Renal Cell Carcinoma. Eur. Urol.81(2), 145–148 (2022).
  • Lanillos J , SantosM, ValdiviaC, MoraA, Rodríguez-AntonaC. Interrogating the Significance of PARP1 Expression and PBRM1 Mutation as Biomarkers for Predicting the Response to Atezolizumab plus Bevacizumab or to Sunitinib in Patients with Clear Cell Renal Cell Carcinoma. Eur. Urol.82(3), 334–335 (2022).
  • Pan YR , WuCE, WangYCet al. Establishment of a novel gene panel as a biomarker of immune checkpoint inhibitor response. Clin. Transl. Immunol.9(7), e1145 (2020).
  • Ricciuti B , RecondoG, SpurrLFet al. Impact of DNA Damage Response and Repair (DDR) Gene Mutations on Efficacy of PD-(L)1 Immune Checkpoint Inhibition in Non-Small Cell Lung Cancer. Clin. Cancer Res.26(15), 4135–4142 (2020).
  • Rizvi H , Sanchez-VegaF, LaKet al. Molecular Determinants of Response to Anti-Programmed Cell Death (PD)-1 and Anti-Programmed Death-Ligand 1 (PD-L1) Blockade in Patients With Non-Small-Cell Lung Cancer Profiled With Targeted Next-Generation Sequencing. J. Clin. Oncol.36(7), 633–641 (2018).
  • Labriola MK , ZhuJ, GuptaRTet al. Characterization of tumor mutation burden, PD-L1 and DNA repair genes to assess relationship to immune checkpoint inhibitors response in metastatic renal cell carcinoma. J. Immunother. Cancer8(1), e000319 (2020).
  • Gibson BA , KrausWL. New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs. Nat. Rev. Mol. Cell Biol.13(7), 411–424 (2012).
  • Pletcher JP , BhattacharjeeS, DoanJPet al. The Emerging Role of Poly (ADP-Ribose) Polymerase Inhibitors as Effective Therapeutic Agents in Renal Cell Carcinoma. Front. Oncol.11, 681441 (2021).
  • Ged G , RifkindI, TonyLet al. ORCHID: a phase II study of Olaparib in Metastatic Renal Cell Carcinoma Patients HarborIng a BAP1 or Other DNA Repair Gene Mutations. Oncologist28(Suppl. 1), S1 (2023).
  • Hamada T , SoongTR, MasugiYet al. TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PD-L1) expression status and tumor-infiltrating lymphocytes in colorectal carcinomas. Oncoimmunology7(7), e1442999 (2018).
  • Jansen CS , ProkhnevskaN, MasterVAet al. An intra-tumoral niche maintains and differentiates stem-like CD8 T cells. Nature576(7787), 465–470 (2019).
  • Eroglu Z , ZaretskyJM, Hu-LieskovanSet al. High response rate to PD-1 blockade in desmoplastic melanomas. Nature553(7688), 347–350 (2018).
  • Johnston MP , KhakooSI. Immunotherapy for hepatocellular carcinoma: current and future. World J. Gastroenterol.25(24), 2977–2989 (2019).
  • Kawashima A , UemuraM, NonomuraN. Importance of Multiparametric Evaluation of Immune-Related T-Cell Markers in Renal-Cell Carcinoma. Clin. Genitourin. Cancer17(6), e1147–e1152 (2019).
  • Zhang S , ZhangE, LongJet al. Immune infiltration in renal cell carcinoma. Cancer Sci.110(5), 1564–1572 (2019).
  • Yao J , XiW, ZhuY, WangH, HuX, GuoJ. Checkpoint molecule PD-1-assisted CD8(+) T lymphocyte count in tumor microenvironment predicts overall survival of patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors. Cancer Manag. Res.10, 3419–3431 (2018).
  • Nakano O , SatoM, NaitoYet al. Proliferative activity of intratumoral CD8(+) T-lymphocytes as a prognostic factor in human renal cell carcinoma: clinicopathologic demonstration of antitumor immunity. Cancer Res.61(13), 5132–5136 (2001).
  • Carlisle JW , JansenCS, CardenasMAet al. Clinical outcome following checkpoint therapy in renal cell carcinoma is associated with a burst of activated CD8 T cells in blood. J. Immunother. Cancer10(7), (2022).
  • Stenzel PJ , SchindeldeckerM, TagschererKEet al. Prognostic and Predictive Value of Tumor-infiltrating Leukocytes and of Immune Checkpoint Molecules PD1 and PDL1 in Clear Cell Renal Cell Carcinoma. Transl. Oncol.13(2), 336–345 (2020).
  • Cristescu R , MoggR, AyersMet al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science362(6411), eaar3593 (2018).
  • Ascierto ML , McmillerTL, BergerAEet al. The Intratumoral Balance between Metabolic and Immunologic Gene Expression Is Associated with Anti-PD-1 Response in Patients with Renal Cell Carcinoma. Cancer Immunol. Res.4(9), 726–733 (2016).
  • Wallin JJ , BendellJC, FunkeRet al. Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma. Nat. Commun.7, 12624 (2016).
  • Routy B , LeChatelier E, DerosaLet al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science359(6371), 91–97 (2018).
  • Salgia NJ , BergerotPG, MaiaMCet al. Stool Microbiome Profiling of Patients with Metastatic Renal Cell Carcinoma Receiving Anti-PD-1 Immune Checkpoint Inhibitors. Eur. Urol.78(4), 498–502 (2020).
  • Pal SK , LiSM, WuXet al. Stool Bacteriomic Profiling in Patients with Metastatic Renal Cell Carcinoma Receiving Vascular Endothelial Growth Factor-Tyrosine Kinase Inhibitors. Clin. Cancer Res.21(23), 5286–5293 (2015).
  • Derosa L , HellmannMD, SpazianoMet al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Ann. Oncol.29(6), 1437–1444 (2018).
  • Dizman N , MezaL, BergerotPet al. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nat. Med.28(4), 704–712 (2022).
  • Shirasu M , TouharaK. The scent of disease: volatile organic compounds of the human body related to disease and disorder. J. Biochem.150(3), 257–266 (2011).
  • Van De Kant KD , VanDer Sande LJ, JöbsisQ, Van SchayckOC, DompelingE. Clinical use of exhaled volatile organic compounds in pulmonary diseases: a systematic review. Respir. Res.13(1), 117 (2012).
  • Janfaza S , KhorsandB, NikkhahM, ZahiriJ. Digging deeper into volatile organic compounds associated with cancer. Biol. Methods Protoc.4(1), bpz014 (2019).
  • Lagniau S , LamoteK, Van MeerbeeckJP, VermaelenKY. Biomarkers for early diagnosis of malignant mesothelioma: do we need another moonshot?Oncotarget8(32), 53751–53762 (2017).
  • Hanna GB , BoshierPR, MarkarSR, RomanoA. Accuracy and Methodologic Challenges of Volatile Organic Compound-Based Exhaled Breath Tests for Cancer Diagnosis: A Systematic Review and Meta-analysis. JAMA Oncol.5(1), e182815 (2019).
  • De Vries R , MullerM, VanDer Noort Vet al. Prediction of response to anti-PD-1 therapy in patients with non-small-cell lung cancer by electronic nose analysis of exhaled breath. Ann. Oncol.30(10), 1660–1666 (2019).
  • Buma AIG , MullerM, DeVries Ret al. eNose analysis for early immunotherapy response monitoring in non-small cell lung cancer. Lung Cancer160, 36–43 (2021).
  • Breathomics as Predictive Biomarker for Checkpoint Inhibitor Response. https://clinicaltrials.gov/study/NCT04146064
  • Stone L . Urinary VOCs as bladder cancer biomarkers. Nat. Rev. Urol.19(5), 256 (2022).
  • Murdocca M , TorinoF, PucciSet al. Urine LOX-1 and Volatilome as Promising Tools towards the Early Detection of Renal Cancer. Cancers (Basel)13(16), (2021).
  • Santoni M , CortelliniA, ButiS. Unlocking the secret of the obesity paradox in renal tumors. Lancet Oncol.21(2), 194–196 (2020).
  • Cortellini A , BersanelliM, SantiniDet al. Another side of the association between body mass index (BMI) and clinical outcomes of cancer patients receiving programmed cell death protein-1 (PD-1)/ Programmed cell death-ligand 1 (PD-L1) checkpoint inhibitors: a multicentre analysis of immune-related adverse events. Eur. J. Cancer128, 17–26 (2020).
  • Sanchez A , FurbergH, KuoFet al. Transcriptomic signatures related to the obesity paradox in patients with clear cell renal cell carcinoma: a cohort study. Lancet Oncol.21(2), 283–293 (2020).
  • Wang Z , AguilarEG, LunaJIet al. Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade. Nat. Med.25(1), 141–151 (2019).
  • Indini A , RijavecE, GhidiniMet al. Impact of BMI on Survival Outcomes of Immunotherapy in Solid Tumors: A Systematic Review. Int. J. Mol. Sci.22(5), 2628 (2021).
  • Martini DJ , ShabtoJM, GoyalSet al. Body Composition as an Independent Predictive and Prognostic Biomarker in Advanced Urothelial Carcinoma Patients Treated with Immune Checkpoint Inhibitors. Oncologist26(12), 1017–1025 (2021).
  • Martini DJ , OlsenTA, GoyalSet al. Body Composition Variables as Radiographic Biomarkers of Clinical Outcomes in Metastatic Renal Cell Carcinoma Patients Receiving Immune Checkpoint Inhibitors. Front. Oncol.11, 707050 (2021).
  • Martini DJ , KlineMR, LiuYet al. Adiposity may predict survival in patients with advanced stage cancer treated with immunotherapy in phase 1 clinical trials. Cancer126(3), 575–582 (2020).
  • Bilen MA , MartiniDJ, LiuYet al. Combined Effect of Sarcopenia and Systemic Inflammation on Survival in Patients with Advanced Stage Cancer Treated with Immunotherapy. Oncologist25(3), e528–e535 (2020).
  • Bagley SJ , KothariS, AggarwalCet al. Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer. Lung Cancer106, 1–7 (2017).
  • Nunno VD , MollicaV, GattoLet al. Prognostic impact of neutrophil-to-lymphocyte ratio in renal cell carcinoma: a systematic review and meta-analysis. Immunotherapy11(7), 631–643 (2019).
  • Templeton AJ , KnoxJJ, LinXet al. Change in Neutrophil-to-lymphocyte Ratio in Response to Targeted Therapy for Metastatic Renal Cell Carcinoma as a Prognosticator and Biomarker of Efficacy. Eur. Urol.70(2), 358–364 (2016).
  • Lalani AA , XieW, MartiniDJet al. Change in Neutrophil-to-lymphocyte ratio (NLR) in response to immune checkpoint blockade for metastatic renal cell carcinoma. J. Immunother. Cancer6(1), 5 (2018).
  • Shao Y , WuB, JiaW, ZhangZ, ChenQ, WangD. Prognostic value of pretreatment neutrophil-to-lymphocyte ratio in renal cell carcinoma: a systematic review and meta-analysis. BMC Urol.20(1), 90 (2020).
  • Bilen MA , RiniBI, VossMHet al. Association of Neutrophil-to-Lymphocyte Ratio with Efficacy of First-Line Avelumab plus Axitinib vs. Sunitinib in Patients with Advanced Renal Cell Carcinoma Enrolled in the Phase 3 JAVELIN Renal 101 Trial. Clin. Cancer Res.28(4), 738–747 (2022).
  • Bilen MA , DutcherGMA, LiuYet al. Association Between Pretreatment Neutrophil-to-Lymphocyte Ratio and Outcome of Patients With Metastatic Renal-Cell Carcinoma Treated With Nivolumab. Clin. Genitourin. Cancer16(3), e563–e575 (2018).
  • Ravindranathan D , MasterVA, BilenMA. Inflammatory Markers in Cancer Immunotherapy. Biology (Basel)10(4), (2021).
  • Bilen MA , MartiniDJ, LiuYet al. The prognostic and predictive impact of inflammatory biomarkers in patients who have advanced-stage cancer treated with immunotherapy. Cancer125(1), 127–134 (2019).
  • Martini DJ , KlineMR, LiuYet al. Novel risk scoring system for metastatic renal cell carcinoma patients treated with cabozantinib. Cancer Treat. Res. Commun.28, 100393 (2021).
  • Zhuang TZ , RavindranathanD, LiuYet al. Baseline Neutrophil-to-Eosinophil Ratio Is Associated with Outcomes in Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors. Oncologist28(3), 239–245 (2023).
  • Brown JT , LiuY, ShabtoJMet al. Modified Glasgow Prognostic Score associated with survival in metastatic renal cell carcinoma treated with immune checkpoint inhibitors. J. Immunother. Cancer9(7), e002851 (2021).
  • Martini DJ , LiuY, ShabtoJMet al. Novel Risk Scoring System for Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors. Oncologist25(3), e484–e491 (2020).
  • Smith CG , MoserT, MouliereFet al. Comprehensive characterization of cell-free tumor DNA in plasma and urine of patients with renal tumors. Genome Med.12(1), 23 (2020).
  • Geertsen L , KoldbyKM, ThomassenM, KruseT, LundL. Circulating Tumor DNA in Patients with Renal Cell Carcinoma. A Systematic Review of the Literature. Eur. Urol. Open Sci.37, 27–35 (2022).
  • Hahn AW , GillDM, MaughanBet al. Correlation of genomic alterations assessed by next-generation sequencing (NGS) of tumor tissue DNA and circulating tumor DNA (ctDNA) in metastatic renal cell carcinoma (mRCC): potential clinical implications. Oncotarget8(20), 33614–33620 (2017).
  • Pal SK , SonpavdeG, AgarwalNet al. Evolution of Circulating Tumor DNA Profile from First-line to Subsequent Therapy in Metastatic Renal Cell Carcinoma. Eur. Urol.72(4), 557–564 (2017).
  • Nikanjam M , KatoS, KurzrockR. Liquid biopsy: current technology and clinical applications. J. Hematol. Oncol.15(1), 131 (2022).
  • Zhang Q , LuoJ, WuSet al. Prognostic and Predictive Impact of Circulating Tumor DNA in Patients with Advanced Cancers Treated with Immune Checkpoint Blockade. Cancer Discov.10(12), 1842–1853 (2020).
  • Yu T , WangY, FanYet al. CircRNAs in cancer metabolism: a review. J. Hematol. Oncol.12(1), 90 (2019).
  • Qu S , LiuZ, YangXet al. The emerging functions and roles of circular RNAs in cancer. Cancer Lett.414, 301–309 (2018).
  • Rashedi S , MardaniM, RafatiAet al. Circular RNAs as prognostic and diagnostic biomarkers in renal cell carcinoma. J. Clin. Lab. Anal.36(10), e24670 (2022).
  • Dong Y , GaoQ, ChenYet al. Identification of CircRNA signature associated with tumor immune infiltration to predict therapeutic efficacy of immunotherapy. Nat. Commun.14(1), 2540 (2023).
  • Franz A , RallaB, WeickmannSet al. Circular RNAs in Clear Cell Renal Cell Carcinoma: Their Microarray-Based Identification, Analytical Validation, and Potential Use in a Clinico-Genomic Model to Improve Prognostic Accuracy. Cancers (Basel)11(10), 1473 (2019).
  • Cui X , WangJ, GuoZet al. Emerging function and potential diagnostic value of circular RNAs in cancer. Mol. Cancer17(1), 123 (2018).
  • Zhang S , ZhangF, NiuY, YuS. Aberration of lncRNA LINC00460 is a Promising Prognosis Factor and Associated with Progression of Clear Cell Renal Cell Carcinoma. Cancer Manag. Res.13, 6489–6497 (2021).
  • Zhou Y , ZhangZ, WoM, XuW. The long non-coding RNA NNT-AS1 promotes clear cell renal cell carcinoma progression via regulation of the miR-137/ Y-box binding protein 1 axis. Bioengineered12(1), 8994–9005 (2021).
  • Li T , TongH, ZhuJet al. Identification of a Three-Glycolysis-Related lncRNA Signature Correlated With Prognosis and Metastasis in Clear Cell Renal Cell Carcinoma. Front. Med. (Lausanne)8, 777507 (2021).
  • Su Y , ZhangT, TangJet al. Construction of Competitive Endogenous RNA Network and Verification of 3-Key LncRNA Signature Associated With Distant Metastasis and Poor Prognosis in Patients With Clear Cell Renal Cell Carcinoma. Front. Oncol.11, 640150 (2021).
  • Zhao M , WangS, LiQ, JiQ, GuoP, LiuX. MALAT1: a long non-coding RNA highly associated with human cancers. Oncol. Lett.16(1), 19–26 (2018).
  • Hirata H , HinodaY, ShahryariVet al. Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205. Cancer Res.75(7), 1322–1331 (2015).
  • Zhai W , MaJ, ZhuRet al. MiR-532-5p suppresses renal cancer cell proliferation by disrupting the ETS1-mediated positive feedback loop with the KRAS-NAP1L1/P-ERK axis. Br. J. Cancer119(5), 591–604 (2018).
  • Jin C , ShiL, LiKet al. Mechanism of tumor-derived extracellular vesicles in regulating renal cell carcinoma progression by the delivery of MALAT1. Oncol. Rep.46(3), 187 (2021).
  • Li Z , MaZ, XuX. Long non-coding RNA MALAT1 correlates with cell viability and mobility by targeting miR-22-3p in renal cell carcinoma via the PI3K/Akt pathway. Oncol. Rep.41(2), 1113–1121 (2019).
  • Guo R , ZouB, LiangYet al. LncRNA RCAT1 promotes tumor progression and metastasis via miR-214-5p/E2F2 axis in renal cell carcinoma. Cell Death Dis.12(7), 689 (2021).
  • Tan L , TangY, LiHet al. N6-Methyladenosine Modification of LncRNA DUXAP9 Promotes Renal Cancer Cells Proliferation and Motility by Activating the PI3K/AKT Signaling Pathway. Front. Oncol.11, 641833 (2021).
  • Nakken S , EikremØ, MartiHPet al. AGAP2-AS1 as a prognostic biomarker in low-risk clear cell renal cell carcinoma patients with progressing disease. Cancer Cell Int.21(1), 690 (2021).
  • Fu S , GongB, WangSet al. Prognostic Value of Long Noncoding RNA DLEU2 and Its Relationship with Immune Infiltration in Kidney Renal Clear Cell Carcinoma and Liver Hepatocellular Carcinoma. Int. J. Gen. Med.14, 8047–8064 (2021).
  • Han S , QiY, XuYet al. lncRNA DLEU2 promotes gastric cancer progression through ETS2 via targeting miR-30a-5p. Cancer Cell Int.21(1), 376 (2021).
  • Dong P , XiongY, KonnoYet al. Long non-coding RNA DLEU2 drives EMT and glycolysis in endometrial cancer through HK2 by competitively binding with miR-455 and by modulating the EZH2/miR-181a pathway. J. Exp. Clin. Cancer Res.40(1), 216 (2021).
  • Li K , SunD, GouQet al. Long non-coding RNA linc00460 promotes epithelial-mesenchymal transition and cell migration in lung cancer cells. Cancer Lett.420, 80–90 (2018).
  • Yue QY , ZhangY. Effects of Linc00460 on cell migration and invasion through regulating epithelial-mesenchymal transition (EMT) in non-small cell lung cancer. Eur. Rev. Med. Pharmacol. Sci.22(4), 1003–1010 (2018).
  • Meng X , SunW, YuJet al. LINC00460-miR-149-5p/miR-150-5p-Mutant p53 Feedback Loop Promotes Oxaliplatin Resistance in Colorectal Cancer. Mol. Ther. Nucleic Acids22, 1004–1015 (2020).
  • Yu Y , ZhangW, LiAet al. Association of Long Noncoding RNA Biomarkers With Clinical Immune Subtype and Prediction of Immunotherapy Response in Patients With Cancer. JAMA Netw. Open3(4), e202149 (2020).
  • Deutsch JS , LipsonEJ, DanilovaLet al. Combinatorial biomarker for predicting outcomes to anti-PD-1 therapy in patients with metastatic clear cell renal cell carcinoma. Cell Rep. Med.4(2), 100947 (2023).
  • Mcdermott DF , HuseniMA, AtkinsMBet al. Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma. Nat. Med.24(6), 749–757 (2018).
  • Bi K , HeMX, BakounyZet al. Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma. Cancer Cell39(5), 649–661.e645 (2021).
  • Das S , JohnsonDB. Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors. J. Immunother. Cancer7(1), 306 (2019).
  • Nukaya T , TakaharaK, YoshizawaAet al. Prognostic Impact of Immune-Related Adverse Events as First-Line Therapy for Metastatic Renal Cell Carcinoma Treated With Nivolumab Plus Ipilimumab: A Multicenter Retrospective Study. Clin. Genitourin. Cancer doi: 10.1016/j.clgc.2023.09.007 (2023).
  • Ueda K , SuekaneS, KuroseHet al. Immune-related adverse events are clinical biomarkers to predict favorable outcomes in advanced renal cell carcinoma treated with nivolumab plus ipilimumab. Jpn. J. Clin. Oncol.52(5), 479–485 (2022).
  • Martini DJ , GoyalS, LiuYet al. Immune-Related Adverse Events as Clinical Biomarkers in Patients with Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors. Oncologist26(10), e1742–e1750 (2021).
  • Washino S , ShirotakeS, TakeshitaHet al. Association between immune-related adverse events and survival in patients with renal cell carcinoma treated with nivolumab plus ipilimumab: immortal time bias-corrected analysis. Int. J. Clin. Oncol.28(12), 1651–1658 (2023).
  • Diehl A , YarchoanM, HopkinsA, JaffeeE, GrossmanSA. Relationships between lymphocyte counts and treatment-related toxicities and clinical responses in patients with solid tumors treated with PD-1 checkpoint inhibitors. Oncotarget8(69), 114268–114280 (2017).
  • Ma Y , MaX, WangJ, WuS, WangJ, CaoB. Absolute eosinophil count may be an optimal peripheral blood marker to identify the risk of immune-related adverse events in advanced malignant tumors treated with PD-1/PD-L1 inhibitors: a retrospective analysis. World J. Surg. Oncol.20(1), 242 (2022).
  • Tasaki Y , HamamotoS, SugiyamaYet al. Elevated eosinophils proportion as predictor of immune-related adverse events after ipilimumab and nivolumab treatment of advanced and metastatic renal cell carcinoma. Int. J. Urol.30(10), 866–874 (2023).
  • Ruste V , GoldschmidtV, LaparraAet al. The determinants of very severe immune-related adverse events associated with immune checkpoint inhibitors: a prospective study of the French REISAMIC registry. Eur. J. Cancer158, 217–224 (2021).
  • Michailidou D , KhakiAR, MorelliMP, DiamantopoulosL, SinghN, GrivasP. Association of blood biomarkers and autoimmunity with immune related adverse events in patients with cancer treated with immune checkpoint inhibitors. Sci. Rep.11(1), 9029 (2021).
  • Eun Y , KimIY, SunJMet al. Risk factors for immune-related adverse events associated with anti-PD-1 pembrolizumab. Sci. Rep.9(1), 14039 (2019).
  • Suazo-Zepeda E , BokernM, VinkePC, HiltermannTJN, DeBock GH, SidorenkovG. Risk factors for adverse events induced by immune checkpoint inhibitors in patients with non-small-cell lung cancer: a systematic review and meta-analysis. Cancer Immunol. Immunother.70(11), 3069–3080 (2021).
  • Lee PY , OenKQX, LimGRSet al. Neutrophil-to-Lymphocyte Ratio Predicts Development of Immune-Related Adverse Events and Outcomes from Immune Checkpoint Blockade: A Case-Control Study. Cancers (Basel)13(6), 1308 (2021).
  • Takada S , MurookaH, TahatsuKet al. Identifying Early Predictive Markers for Immune-Related Adverse Events in Nivolumab-Treated Patients with Renal Cell Carcinoma and Gastric Cancer. Asian Pac. J. Cancer Prev.23(2), 695–701 (2022).
  • Kizawa R , KunoM, WashinoSet al. 142P The predictive biomarker for immune-related adverse events (irAEs) in patients with metastatic renal cell carcinoma treated with the combination therapy of nivolumab plus ipilimumab: musashino study-irAE. Ann. Oncol.33, S1488 (2022).
  • Khan S , KhanSA, LuoXet al. Immune dysregulation in cancer patients developing immune-related adverse events. Br. J. Cancer120(1), 63–68 (2019).
  • Tahir SA , GaoJ, MiuraYet al. Autoimmune antibodies correlate with immune checkpoint therapy-induced toxicities. Proc. Natl Acad. Sci. USA116(44), 22246–22251 (2019).
  • Les I , MartínezM, NarroAet al. Association of immune-related adverse events induced by nivolumab with a battery of autoantibodies. Ann. Med.53(1), 762–769 (2021).
  • Barth DA , StanzerS, SpiegelbergJet al. Evaluation of autoantibodies as predictors of treatment response and immune-related adverse events during the treatment with immune checkpoint inhibitors: a prospective longitudinal pan-cancer study. Cancer Med.11(16), 3074–3083 (2022).
  • Bukhari S , HenickBS, WinchesterRJet al. Single-cell RNA sequencing reveals distinct T cell populations in immune-related adverse events of checkpoint inhibitors. Cell Rep. Med.4(1), 100868 (2023).
  • Kobayashi T , NagataM, IkehataYet al. T-Cell Receptor Repertoire as a Predictor of Immune-Related Adverse Events in Renal Cell Carcinoma. Curr. Issues Mol. Biol.45(11), 8939–8949 (2023).
  • Liguori L , LucianoA, PolcaroGet al. Prior Anti-Angiogenic TKI-Based Treatment as Potential Predisposing Factor to Nivolumab-Mediated Recurrent Thyroid Disorder Adverse Events in mRCC Patients: A Case Series. Biomedicines11(11), 2974 (2023).
  • He S , WangL, SunY, DuH, YuX. Case Report: successful immune checkpoint inhibitor-based rechallenge in a patient with advanced renal clear cell cancer. Front. Immunol.14, 1270828 (2023).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.