2025
Intratumoral IL12 mRNA administration activates innate and adaptive pathways in checkpoint inhibitor-resistant tumors resulting in complete responses
Lakshmipathi J, Santha S, Li M, Qian Y, Roy S, Luheshi N, Politi K, Bosenberg M, Eyles J, Muthusamy V. Intratumoral IL12 mRNA administration activates innate and adaptive pathways in checkpoint inhibitor-resistant tumors resulting in complete responses. Cancer Immunology, Immunotherapy 2025, 74: 250. PMID: 40560386, PMCID: PMC12198101, DOI: 10.1007/s00262-025-04105-0.Peer-Reviewed Original ResearchThis study investigates intratumoral IL12 mRNA therapy, showing it effectively reactivates immune responses in checkpoint inhibitor-resistant tumors, leading to significant complete responses, potentially benefiting cancer patients with resistant tumors.Artificial Intelligence Algorithm Predicts Response to Immune Checkpoint Inhibitors.
Fa'ak F, Coudray N, Jour G, Ibrahim M, Illa-Bochaca I, Qiu S, Claudio Quiros A, Yuan K, Johnson D, Rimm D, Weber J, Tsirigos A, Osman I. Artificial Intelligence Algorithm Predicts Response to Immune Checkpoint Inhibitors. Clinical Cancer Research 2025 PMID: 40553453, DOI: 10.1158/1078-0432.ccr-24-3720.Peer-Reviewed Original ResearchResponse to ICIImmune checkpoint inhibitorsMetastatic melanoma cohortCheckpoint inhibitorsMelanoma cohortMelanoma treated with immune checkpoint inhibitorsBiomarkers of ICI responseImmune checkpoint inhibitor useImmune checkpoint inhibitor treatmentCohort of melanoma patientsLow tumor stroma ratioProgression-free survivalTumor-stroma ratioSignificant adverse eventsArea under the curvePatient overall survivalMetastatic settingUnresectable melanomaEpithelioid histologyICI responseMelanoma patientsMetastatic melanomaOverall survivalPatient survivalTumor featuresIntegrated Immune Landscape Analysis of RNA Splicing Factor-Mutant AML and Higher risk MDS Treated with Azacitidine ± Durvalumab
Bewersdorf J, Hasle V, Shallis R, Thompson E, de Menezes D, Rose S, Boss I, Mendez L, Podoltsev N, Stahl M, Kewan T, Halene S, Haferlach T, Fox B, Zeidan A. Integrated Immune Landscape Analysis of RNA Splicing Factor-Mutant AML and Higher risk MDS Treated with Azacitidine ± Durvalumab. Therapeutic Advances In Hematology 2025, 16: 20406207251347344. PMID: 40546817, PMCID: PMC12182606, DOI: 10.1177/20406207251347344.Peer-Reviewed Original ResearchThis study investigates the immune landscape of RNA splicing factor-mutant AML and MDS, showing no survival benefit from adding durvalumab to azacitidine treatment.Incidence and predictors of immune checkpoint inhibitor treatment–related cognitive impairment in a racial and ethnic diverse population
Sayer M, Agrawal P, Ng D, Kagramanov D, Trudeau J, Othy S, Acharya M, Chan A. Incidence and predictors of immune checkpoint inhibitor treatment–related cognitive impairment in a racial and ethnic diverse population. Supportive Care In Cancer 2025, 33: 523. PMID: 40451933, PMCID: PMC12127230, DOI: 10.1007/s00520-025-09560-0.Peer-Reviewed Original ResearchConceptsIntroductionImmune checkpoint inhibitorsTherapy initiationPatient-reported outcomesGeneralized Estimating EquationsSignificant cognitive impairmentICI-treated patientsAnti-cancer immunityClinically significant cognitive impairmentCognitive functionCognitive impairmentTreatment-related cognitive impairmentPhysical functionCheckpoint inhibitorsMild to severe symptomsImpaired physical functionRisk patientsImmune dysregulationConcurrent symptomsInflammatory biomarkersPatient characteristicsSymptom scoresCancer therapyCognitive function scoresT-scoreTherapyEffect of elevated expression of LILRB4 and TSC22D3 on survival in lung cancer.
Hrinczenko B, Adeyelu T, Wei W, Elliott A, Bepler G, Vanderwalde A, Halmos B, Antonarakis E, Lustberg M, Jacob J. Effect of elevated expression of LILRB4 and TSC22D3 on survival in lung cancer. Journal Of Clinical Oncology 2025, 43: 2633-2633. DOI: 10.1200/jco.2025.43.16_suppl.2633.Peer-Reviewed Original ResearchNon-small cell lung cancerSmall cell lung cancerImmune checkpoint inhibitorsMetastatic non-small cell lung cancerProgression-free survivalCell lung cancerOverall survivalLung cancerLILRB4 expressionICI responsePrimary non-small cell lung cancerMetastatic small cell lung cancerSuppress adaptive immune responsesAssociated with improved survivalICI-treated patientsAssociated with OSImprove survival outcomesAdaptive immune responsesLung cancer typesDatasets of non-small cell lung cancerAnti-inflammatory pathwayLung cancer survivalAtezolizumab treatmentTSC22D3 expressionCheckpoint inhibitorsInvestigation of tumor-associated macrophages (TAMs) and therapeutic resistance to immune checkpoint inhibitors (ICI) through single-cell analysis of renal cell carcinoma (RCC).
Kashima S, Rout R, Hugaboom M, Ye Z, Schindler N, Malik R, Dighe A, Sun M, Lee G, Xu W, Signoretti S, Schoenfeld D, Hurwitz M, Adeniran A, Humphrey P, Kenney P, McGregor B, McKay R, Choueiri T, Braun D. Investigation of tumor-associated macrophages (TAMs) and therapeutic resistance to immune checkpoint inhibitors (ICI) through single-cell analysis of renal cell carcinoma (RCC). Journal Of Clinical Oncology 2025, 43: 4527-4527. DOI: 10.1200/jco.2025.43.16_suppl.4527.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsTumor-associated macrophagesRenal cell carcinomaICI-based therapyRCC tumor microenvironmentTumor microenvironmentNon-respondersGene programResistance to immune checkpoint inhibitorsImmune checkpoint inhibitor resistanceTumor-associated macrophage populationSuppress antitumor immunityWilcoxon Signed Rank TestInterferon-stimulated genesMechanisms of resistanceCheckpoint inhibitorsAntitumor immunityStable diseaseSystemic therapyCombination therapyCell carcinomaPotential therapeutic targetTreatment resistanceAntigen presentationTumor samplesLifileucel in patients with advanced melanoma: 5-year outcomes of the C-144-01 study.
Medina T, Chesney J, Kluger H, Hamid O, Whitman E, Cusnir M, Thomas S, Wermke M, Domingo-Musibay E, Phan G, Kirkwood J, Larkin J, Weber J, Finckenstein F, Chou J, Gastman B, Sulur G, Wu R, Fiaz R, Sarnaik A. Lifileucel in patients with advanced melanoma: 5-year outcomes of the C-144-01 study. Journal Of Clinical Oncology 2025, 43: 9515-9515. DOI: 10.1200/jco.2025.43.16_suppl.9515.Peer-Reviewed Original ResearchDuration of responseAnti-PD-1/PD-L1 therapyAdvanced melanomaFollow-upOverall survivalEastern Cooperative Oncology Group performance statusAnti-PD-1/PD-L1Autologous T-cell immunotherapyMedian duration of responseTreatment-emergent adverse eventsDoses of interleukin-2Treatment of adult patientsImmune checkpoint inhibitorsT-cell immunotherapyTumor-infiltrating lymphocytesDurability of responseLong-term safety concernsOpen-label studyStudy follow-upGroup of ptsMedian OSRefractory melanomaCheckpoint inhibitorsOS ratesRECIST v1.1Gut-associated checkpoint as a prognostic biomarker in metastatic renal cell carcinoma (mRCC): Results from a randomized first-line clinical trial.
Saliby R, Machaalani M, Zhong C, Alves Costa Silva C, Labaki C, Saad E, Steiner C, Yekeduz E, Eid M, Daoud Khatoun W, Sun M, Cai T, Braun D, Xu W, Derosa L, Lee G, Xie W, Albiges L, Zitvogel L, Choueiri T. Gut-associated checkpoint as a prognostic biomarker in metastatic renal cell carcinoma (mRCC): Results from a randomized first-line clinical trial. Journal Of Clinical Oncology 2025, 43: 4512-4512. DOI: 10.1200/jco.2025.43.16_suppl.4512.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaProgression-free survivalRestricted cubic splinesSMAdCAM-1Immune checkpoint inhibitorsOverall survivalCox regression modelsGut dysbiosisAssociated with progression-free survivalAnti-cancer immune responseOptimal cut-off valueICI-based therapyIMDC risk groupsRenal cell carcinomaCut-off valueRestricted cubic spline plotsLog-rank statisticsJAVELIN RenalCheckpoint inhibitorsOS ratesOS outcomesCell carcinomaPrognostic valueLuminex assayClinical outcomesCo-expression network-based analysis of gene programs contributing to immune checkpoint inhibitor (ICI) resistance in renal cell carcinoma (RCC).
Malik R, Rout R, Kashima S, Saad E, Kane H, Shah V, Hugaboom M, Ye Z, Schindler N, Dighe A, Sun M, Lee G, Xu W, Signoretti S, McGregor B, McKay R, Atkins M, Van Allen E, Choueiri T, Braun D. Co-expression network-based analysis of gene programs contributing to immune checkpoint inhibitor (ICI) resistance in renal cell carcinoma (RCC). Journal Of Clinical Oncology 2025, 43: 4530-4530. DOI: 10.1200/jco.2025.43.16_suppl.4530.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRenal cell carcinomaImmune cellsImmune infiltrationSignature scoreRCC tumor microenvironmentResistance to immune checkpoint inhibitorsAssociated with worse PFSICI-based therapyScRNA-seq dataGene programCD8+ TPhase II trialICI resistanceImmune-lowCheckpoint inhibitorsRibosomal proteinsCD4+II trialPrognostic roleRenal cell carcinoma tumor sampleRNA-seqCell carcinomaTumor microenvironmentScRNA-seqAssessment of time-to-treatment-failure (TTF) as a surrogate endpoint for overall survival (OS) to immune checkpoint inhibitor (ICI) regimens in metastatic renal cell carcinoma (mRCC): Findings from an IMDC analysis.
Yochum Z, Saliby R, Xie W, Moritz V, Wells C, Ferrier E, Zarba M, Ebrahimi H, Suárez C, Ruiz-Morales J, McKay R, Powles T, Wood L, Lalani A, Pal S, de Velasco G, Takemura K, Agarwal N, Heng D, Choueiri T. Assessment of time-to-treatment-failure (TTF) as a surrogate endpoint for overall survival (OS) to immune checkpoint inhibitor (ICI) regimens in metastatic renal cell carcinoma (mRCC): Findings from an IMDC analysis. Journal Of Clinical Oncology 2025, 43: 4528-4528. DOI: 10.1200/jco.2025.43.16_suppl.4528.Peer-Reviewed Original ResearchMetastatic renal cell carcinomaInternational mRCC Database ConsortiumImmune checkpoint inhibitorsMetastatic renal cell carcinoma patientsICI-based regimensOverall survivalFollow-upIntermediate endpointsTreatment failureSub-cohortLandmark analysisICI startMedian Follow-UpEvent-free ratePhase III trialsKaplan-Meier methodFollow-up timeRenal cell carcinomaMultivariate Cox regressionPotential intermediate endpointCheckpoint inhibitorsCell histologyDrug cessationTherapy initiationIII trialsCirculating immunoregulatory B cell and autoreactive antibody profiles predict lack of toxicity to anti-PD-1 checkpoint inhibitor treatment in advanced melanoma
Willsmore Z, Booth L, Patel A, Di Meo A, Prassas I, Chauhan J, Wu Y, Fitzpartick A, Stoker K, Kapiris M, Biswas D, Perucha E, Whittaker S, Tsoka S, Diamandis E, Middleton G, Tull T, Papa S, Lacy K, Karagiannis S. Circulating immunoregulatory B cell and autoreactive antibody profiles predict lack of toxicity to anti-PD-1 checkpoint inhibitor treatment in advanced melanoma. Journal For ImmunoTherapy Of Cancer 2025, 13: e011682. PMID: 40449958, PMCID: PMC12142029, DOI: 10.1136/jitc-2025-011682.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsAnti-PD-1 therapyStage III/IV melanomaAnti-PD-1Memory B cellsB cellsCheckpoint inhibitorsHigher IgG4Development of immune-related adverse eventsResponse to anti-PD-1 therapyClass-switched memory B cellsClass-switched B cellsAccurate predictive biomarkersDN2 B cellsExtrafollicular B cell responseCheckpoint inhibitor treatmentB cell frequenciesB cell responsesIL-10+Response to therapyIgE serum levelsImmune response profileHumoral immune response profileSerum antibody isotypesAdvanced melanomaImmune checkpoint inhibitor (ICI) efficacy in triple-negative breast cancer (TNBC) patients with liver metastases (LM): A meta-analysis.
Park D, Abid M, Lustberg M, Kalinski P, Gandhi S, Huang C. Immune checkpoint inhibitor (ICI) efficacy in triple-negative breast cancer (TNBC) patients with liver metastases (LM): A meta-analysis. Journal Of Clinical Oncology 2025, 43: e13131-e13131. DOI: 10.1200/jco.2025.43.16_suppl.e13131.Peer-Reviewed Original ResearchProgrammed death-ligand1Triple-negative breast cancerImmune checkpoint inhibitorsProgression free survivalLiver metastasesHazard ratioBreast cancerEfficacy of immune checkpoint inhibitorsTriple-negative breast cancer casesLog-transformed hazard ratioProgression free survival benefitImmune checkpoint inhibitor therapyAssociated with poor prognosisSite of diseaseAggressive breast cancerMeta-analysisArea of translational researchRandom-effects modelCheckpoint inhibitorsRandomized Controlled TrialsSystematic literature searchFree survivalOverall survivalDistant metastasisImmunocompromised stateTargeting Neuronal Nitric Oxide Synthase (nNOS) as a Novel Approach to Enhancing the Anti-Melanoma Activity of Immune Checkpoint Inhibitors
Patel A, Tong S, Lozada K, Awasthi A, Silverman R, Totonchy J, Yang S. Targeting Neuronal Nitric Oxide Synthase (nNOS) as a Novel Approach to Enhancing the Anti-Melanoma Activity of Immune Checkpoint Inhibitors. Pharmaceutics 2025, 17: 691. PMID: 40574005, PMCID: PMC12196278, DOI: 10.3390/pharmaceutics17060691.Peer-Reviewed Original ResearchPeripheral blood mononuclear cellsNeuronal nitric oxide synthaseNeuronal nitric oxide synthase inhibitorActivity of immune checkpoint inhibitorsT cell activationImmune checkpoint inhibitorsAnti-melanoma activityT cellsTargeting nNOSNitric oxide synthaseCheckpoint inhibitorsIFN-gCD8<sup>+</sup>PD-1<sup>+</sup> T cellsInterleukin-2PD-1<sup>+</sup> T cellsEffects of nNOS inhibitionIL-2-secreting T cellsImmune responseMouse peripheral blood mononuclear cellsOxide synthaseAnti-PD-1Immune checkpoint blockadeMelanoma immune responsePD-1 blockadePD-L1 expressionAssociation of DNA damage response signals and oxidative stress status with nivolumab efficacy in patients with Head and Neck Squamous Cell Carcinoma
Papanikolaou C, Economopoulou P, Spathis A, Kotsantis I, Gavrielatou N, Anastasiou M, Moutafi M, Kyriazoglou A, Foukas G, Lelegiannis I, Rimm D, Panayiotides I, Foukas P, Souliotis V, Psyrri A. Association of DNA damage response signals and oxidative stress status with nivolumab efficacy in patients with Head and Neck Squamous Cell Carcinoma. British Journal Of Cancer 2025, 1-12. PMID: 40410274, DOI: 10.1038/s41416-025-03032-2.Peer-Reviewed Original ResearchHead and neck squamous cell carcinomaPeripheral blood mononuclear cellsNeck squamous cell carcinomaSquamous cell carcinomaCell carcinomaNon-respondersHead and neck squamous cell carcinoma patientsResponse to immune checkpoint inhibitorsRecurrent/metastatic HNSCC patientsImmune checkpoint inhibitorsResponse to nivolumabDesign of clinical trialsBlood mononuclear cellsOxidative stressDNA repair capacityNon-invasive biomarkersNivolumab efficacyNivolumab therapyNivolumab trialsCheckpoint inhibitorsHNSCC patientsOxidative stress statusMethodsOxidative stressMacrophage compartmentMononuclear cellsPartial mitochondrial involvement in the antiproliferative and immunostimulatory effects of PT-112
Soler-Agesta R, Beltrán-Visiedo M, Sato A, Yamazaki T, Guilbaud E, Yim C, Congenie M, Ames T, Anel A, Galluzzi L. Partial mitochondrial involvement in the antiproliferative and immunostimulatory effects of PT-112. OncoImmunology 2025, 14: 2507245. PMID: 40386940, PMCID: PMC12091903, DOI: 10.1080/2162402x.2025.2507245.Peer-Reviewed Original ResearchConceptsImmunogenic cell deathTS/A cellsPD-L1Immune checkpoint inhibitorsExposure of calreticulinLigand PD-L1Type I IFN secretionSecrete type I IFNsRelease of HMGB1MHC class IMHC class I moleculesClass I moleculesType I IFNImmunostimulatory signalsCheckpoint inhibitorsCell surfaceTreatment discontinuationClinical responsePreclinical modelsMalignant cellsSolid tumorsTumor typesColorectal carcinomaGenetic alterationsHMGB1 releaseThe treatment of cutaneous immune-related adverse events from immune checkpoint inhibitors with biologic therapy: A single-institution retrospective study at a tertiary care cancer center
Greenberg A, Valido K, Vesely M, Leventhal J. The treatment of cutaneous immune-related adverse events from immune checkpoint inhibitors with biologic therapy: A single-institution retrospective study at a tertiary care cancer center. Journal Of The American Academy Of Dermatology 2025 PMID: 40345549, DOI: 10.1016/j.jaad.2025.04.075.Peer-Reviewed Original ResearchMitochondrial gene SLC25A24 regulated anti-tumor immunity and inhibited the proliferation and metastasis of colorectal cancer by PKG1-dependent cGMP/PKG1 pathway
Gao Y, Peng Y, Zhou Y, Zhu J, Fu S, Chen Y, Cai C, Han Y, Shen H, Zeng S, Mao L, Xiao Z. Mitochondrial gene SLC25A24 regulated anti-tumor immunity and inhibited the proliferation and metastasis of colorectal cancer by PKG1-dependent cGMP/PKG1 pathway. International Immunopharmacology 2025, 157: 114664. PMID: 40334626, DOI: 10.1016/j.intimp.2025.114664.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsAnti-tumor immunityColorectal cancerResponse to immune checkpoint inhibitorsAssociated with worse overall survivalKaplan-Meier survival analysisProgression-free survivalTumor immune regulationMetastasis of colorectal cancerMitochondrial solute carriersMicrosatellite instabilityColorectal cancer cell linesColorectal cancer patientsCancer-related mortalityProliferation-related markersCheckpoint inhibitorsColorectal cancer progressionOverall survivalImmune infiltrationPotential therapeutic targetPrognostic markerUnfavorable prognosisColorectal cancer tissuesImmune regulationClinical cohortA phase 2 trial of pembrolizumab for recurrent Lynch-like versus sporadic endometrial cancers with microsatellite instability (NCT02899793): Updated survival and response analyses
Ettorre V, Bellone S, Greenman M, McNamara B, Palmieri L, Sethi N, Demirkiran C, Papatla K, Kailasam A, Siegel E, Ratner E, Santin A. A phase 2 trial of pembrolizumab for recurrent Lynch-like versus sporadic endometrial cancers with microsatellite instability (NCT02899793): Updated survival and response analyses. Gynecologic Oncology 2025, 197: 110-115. PMID: 40334308, DOI: 10.1016/j.ygyno.2025.04.591.Peer-Reviewed Original ResearchProgression free survivalWhole-exome sequencingImmune checkpoint inhibitorsOverall survivalEndometrial cancerMicrosatellite instability-highCheckpoint inhibitorsFree survivalFollow-upResponse to immune checkpoint inhibitorsPatients treated with pembrolizumabProspective phase II studyExome sequencingResponse rateRecurrent platinum-resistantPhase II studyPhase 2 trialOverall survival dataEndometrial cancer patientsMLH-1MSI-H patientsFoundationOne platformImproved OSUpdate survivalPrognostic significanceCharacterizing Chronic Cutaneous Immune-Related Adverse Events Following Immune Checkpoint Inhibitors
Fletcher K, Goodman R, Lawless A, Woodford R, Fa’ak F, Tipirneni A, Patrinely J, Yeoh H, Rapisuwon S, Haydon A, Osman I, Mehnert J, Long G, Sullivan R, Carlino M, Menzies A, Dewan A, Johnson D. Characterizing Chronic Cutaneous Immune-Related Adverse Events Following Immune Checkpoint Inhibitors. JAMA Dermatology 2025, 161: 555-557. PMID: 40072456, PMCID: PMC11904794, DOI: 10.1001/jamadermatol.2025.0025.Peer-Reviewed Original ResearchThe Current and Future of Biomarkers of Immune Related Adverse Events
Bracamonte-Baran W, Kim S. The Current and Future of Biomarkers of Immune Related Adverse Events. Immunology And Allergy Clinics Of North America 2025, 45: 223-249. PMID: 40287170, DOI: 10.1016/j.iac.2025.01.010.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsImmune-related adverse eventsAdverse eventsMechanism of action of immune checkpoint inhibitorsImmune related adverse eventsAssociated with life-threateningRelated adverse eventsCheckpoint inhibitorsClinical responseReview biomarkersStratify riskLife-threateningCancer therapeuticsCancer
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