2025
Top advances of the year: Small cell lung cancer
Shields M, Chiang A, Byers L. Top advances of the year: Small cell lung cancer. Cancer 2025, 131: e35770. PMID: 40040254, DOI: 10.1002/cncr.35770.Peer-Reviewed Original ResearchConceptsSmall cell lung cancerExtensive-stage small cell lung cancerCell lung cancerLung cancerLimited-stage small cell lung cancerFrequency of disease relapseTiming of immunotherapyCancer-related mortalityLong-term survivalAntibody-drug conjugatesNeuroendocrine subtypeDisease relapseAggressive biologyMetastatic spreadInferior outcomesImproved survivalImmunotherapyTherapeutic breakthroughConsolidation treatmentCancerPrecision medicineBiomarker selectionSurvivalLurbinectedinForward-thinking approachSensitive detection of synthetic response to cancer immunotherapy driven by gene paralog pairs
Dong C, Zhang F, He E, Ren P, Verma N, Zhu X, Feng D, Cai J, Zhao H, Chen S. Sensitive detection of synthetic response to cancer immunotherapy driven by gene paralog pairs. Patterns 2025, 6: 101184. DOI: 10.1016/j.patter.2025.101184.Peer-Reviewed Original ResearchParalogous gene pairsParalogous pairsChimeric antigen receptor T cellsResponse to cancer immunotherapyDouble knockoutCancer immunotherapy responseGene pairsCheckpoint blockadeGenome-wide screenImmunotherapy efficacyCancer immunotherapyEnhance immunotherapyImmunotherapy responseImmunotherapy effectT cellsImmunotherapyCancer treatmentIndividual genesCRISPR screensEnrichment analysisParalogsCancerTreatmentCombined targetFunctional significanceProceedings of the National Cancer Institute Workshop on combining immunotherapy with radiotherapy: challenges and opportunities for clinical translation
Morris Z, Demaria S, Monjazeb A, Formenti S, Weichselbaum R, Welsh J, Enderling H, Schoenfeld J, Brody J, McGee H, Mondini M, Kent M, Young K, Galluzzi L, Karam S, Theelen W, Chang J, Huynh M, Daib A, Pitroda S, Chung C, Serre R, Grassberger C, Deng J, Sodji Q, Nguyen A, Patel R, Krebs S, Kalbasi A, Kerr C, Vanpouille-Box C, Vick L, Aguilera T, Ong I, Herrera F, Menon H, Smart D, Ahmed J, Gartrell R, Roland C, Fekrmandi F, Chakraborty B, Bent E, Berg T, Hutson A, Khleif S, Sikora A, Fong L. Proceedings of the National Cancer Institute Workshop on combining immunotherapy with radiotherapy: challenges and opportunities for clinical translation. The Lancet Oncology 2025, 26: e152-e170. PMID: 40049206, DOI: 10.1016/s1470-2045(24)00656-9.Peer-Reviewed Original ResearchConceptsAnti-tumor immune responseDelivery of radiotherapyTumor immune recognitionSelection of immunotherapyBiomarker-guided approachesNational Cancer Institute workshopClinical trial dataImmunotherapy combinationsClinical responseImprove patient outcomesPreclinical modelsPatient selectionRadiotherapyImmunotherapyClinical endpointsClinical dataClinical studiesImmune recognitionImmune responseImmune effectsAnimal studiesClinical translationPatient outcomesTrial dataNegative trialsHIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy
Jiang Q, Braun D, Clauser K, Ramesh V, Shirole N, Duke-Cohan J, Nabilsi N, Kramer N, Forman C, Lippincott I, Klaeger S, Phulphagar K, Chea V, Kim N, Vanasse A, Saad E, Parsons T, Carr-Reynolds M, Carulli I, Pinjusic K, Jiang Y, Li R, Syamala S, Rachimi S, Verzani E, Stevens J, Lane W, Camp S, Meli K, Pappalardi M, Herbert Z, Qiu X, Cejas P, Long H, Shukla S, Van Allen E, Choueiri T, Churchman L, Abelin J, Gurer C, MacBeath G, Childs R, Carr S, Keskin D, Wu C, Kaelin W. HIF regulates multiple translated endogenous retroviruses: Implications for cancer immunotherapy. Cell 2025 PMID: 40023154, DOI: 10.1016/j.cell.2025.01.046.Peer-Reviewed Original ResearchClear cell renal cell carcinomaCancer immunotherapyAntigen-specific T cell responsesAllogeneic stem cell transplantationEndogenous retrovirusesClear cell renal cell carcinoma patientsLow mutational burdenCell renal cell carcinomaStem cell transplantationT cell responsesRenal cell carcinomaVHL tumor suppressor geneTumor suppressor geneHLA-bound peptidesEndogenous retrovirus expressionNon-ccRCCCell transplantationMutational burdenSpontaneous regressionCell carcinomaT cellsCase reportSuppressor geneHIF transcription factorsImmunotherapyAuthor Correction: Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy
Zhang F, Chow R, He E, Dong C, Xin S, Mirza D, Feng Y, Tian X, Verma N, Majety M, Zhang Y, Wang G, Chen S. Author Correction: Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy. Nature Biotechnology 2025, 1-1. PMID: 39901026, DOI: 10.1038/s41587-025-02576-1.Peer-Reviewed Original ResearchMitochondrial succinate feeds T cell exhaustion in cancer
Galluzzi L, Guilbaud E, Garg A. Mitochondrial succinate feeds T cell exhaustion in cancer. Cancer Cell 2025, 43: 168-170. PMID: 39933894, DOI: 10.1016/j.ccell.2025.01.005.Peer-Reviewed Original ResearchMultiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy
Zhang F, Chow R, He E, Dong C, Xin S, Mirza D, Feng Y, Tian X, Verma N, Majety M, Zhang Y, Wang G, Chen S. Multiplexed inhibition of immunosuppressive genes with Cas13d for combinatorial cancer immunotherapy. Nature Biotechnology 2025, 1-14. PMID: 39820813, DOI: 10.1038/s41587-024-02535-2.Peer-Reviewed Original ResearchAdeno-associated virusTumor microenvironmentImmunosuppressive genesAntitumor efficacyCD8+ T cell infiltrationIn vivo antitumor efficacyCombinatorial cancer immunotherapyImmunosuppressive tumor microenvironmentSyngeneic tumor modelsT cell infiltrationTumor microenvironment remodelingMulti-agent combinationsMultiple tumor typesAntitumor immunityCombinatorial immunotherapyOptimal immunotherapyCancer immunotherapyGene alterationsTumor typesTumor modelReduced neutrophilLiver toxicityShRNA treatmentWhole-transcriptome profilingImmunotherapyAutogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial
Lopez J, Powles T, Braiteh F, Siu L, LoRusso P, Friedman C, Balmanoukian A, Gordon M, Yachnin J, Rottey S, Karydis I, Fisher G, Schmidt M, Schuler M, Sullivan R, Burris H, Galvao V, Henick B, Dirix L, Jaeger D, Ott P, Wong K, Jerusalem G, Schiza A, Fong L, Steeghs N, Leidner R, Rittmeyer A, Laurie S, Gort E, Aljumaily R, Melero I, Sabado R, Rhee I, Mancuso M, Muller L, Fine G, Yadav M, Kim L, Leveque V, Robert A, Darwish M, Qi T, Zhu J, Zhang J, Twomey P, Rao G, Low D, Petry C, Lo A, Schartner J, Delamarre L, Mellman I, Löwer M, Müller F, Derhovanessian E, Cortini A, Manning L, Maurus D, Brachtendorf S, Lörks V, Omokoko T, Godehardt E, Becker D, Hawner C, Wallrapp C, Albrecht C, Kröner C, Tadmor A, Diekmann J, Vormehr M, Jork A, Paruzynski A, Lang M, Blake J, Hennig O, Kuhn A, Sahin U, Türeci Ö, Camidge D. Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial. Nature Medicine 2025, 31: 152-164. PMID: 39762422, PMCID: PMC11750724, DOI: 10.1038/s41591-024-03334-7.Peer-Reviewed Original ResearchConceptsCD8+ T cellsAdvanced solid tumorsT cellsSolid tumorsCirculating CD8+ T cellsEfficacy of cancer immunotherapyTumor-infiltrating T cellsStimulate T cell responsesResponse to immunotherapyT cell responsesPreliminary antitumor activityPhase 1 studyPhase 1 trialDose escalationPretreated patientsCancer immunotherapyEvaluation of pharmacokineticsCD4+Tumor lesionsTreatment initiationTumor tissuesAtezolizumabClinical activityDisease characteristicsImmunotherapy
2024
A novel pharmacological entity toward integrated multimodal immunotherapy
Sirera R, Beltrán-Visiedo M, Galluzzi L. A novel pharmacological entity toward integrated multimodal immunotherapy. Trends In Pharmacological Sciences 2024, 46: 95-97. PMID: 39721827, DOI: 10.1016/j.tips.2024.12.001.Peer-Reviewed Original ResearchImmunogenicity of cell death and cancer immunotherapy with immune checkpoint inhibitors
Catanzaro E, Beltrán-Visiedo M, Galluzzi L, Krysko D. Immunogenicity of cell death and cancer immunotherapy with immune checkpoint inhibitors. Cellular & Molecular Immunology 2024, 22: 24-39. PMID: 39653769, PMCID: PMC11685666, DOI: 10.1038/s41423-024-01245-8.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsImmunogenic cell deathImmunogenic cell death inducerCheckpoint inhibitorsRefractory to immune checkpoint inhibitorsImmunogenicity of cell deathFraction of patientsCombinatorial treatment strategiesAdaptive immune responsesCell deathCombinatorial partnersCancer immunotherapyCombinatorial regimensClinical findingsClinical managementTreatment strategiesClinical activityImmune responseImmunotherapyPatientsCancerOncology settingInhibitorsDeathInducerLactate fermentation intoxicates TILs
Hunt B, Kessler E, Joshi N. Lactate fermentation intoxicates TILs. Nature Immunology 2024, 25: 2176-2177. PMID: 39516647, DOI: 10.1038/s41590-024-02020-7.Peer-Reviewed Original Research109 Development of a novel immuno-metabolic spatial signature to predict response and resistance to immunotherapy in NSCLC patients
Markovits E, Monkman J, Aung T, Reeves J, O’Byrne K, Czertock R, Puig O, Rimm D, Kulasinghe A. 109 Development of a novel immuno-metabolic spatial signature to predict response and resistance to immunotherapy in NSCLC patients. 2024, a119-a119. DOI: 10.1136/jitc-2024-sitc2024.0109.Peer-Reviewed Original ResearchInterventional Oncology Meets Immuno-oncology: Combination Therapies for Hepatocellular Carcinoma.
Bitar R, Salem R, Finn R, Greten T, Goldberg S, Chapiro J. Interventional Oncology Meets Immuno-oncology: Combination Therapies for Hepatocellular Carcinoma. Radiology 2024, 313: e232875. PMID: 39560477, PMCID: PMC11605110, DOI: 10.1148/radiol.232875.Peer-Reviewed Original ResearchConceptsManagement of hepatocellular carcinomaHepatocellular carcinomaLocoregional therapyClinical trialsImage-guided locoregional therapiesEnd pointsStages of hepatocellular carcinomaTumor microenvironment mechanismsCatheter-directed therapyCombination of immunotherapyProspective clinical trialImaging end pointsStandard of careAdjuvant settingNovel immunotherapiesCombination therapyTherapy resistanceInterventional radiologistsImmunotherapyDisease stageTherapyDisease evolutionNovel biomarkersCarcinomaMicroenvironment mechanismsEpitope-anchored contrastive transfer learning for paired CD8+ T cell receptor–antigen recognition
Zhang Y, Wang Z, Jiang Y, Littler D, Gerstein M, Purcell A, Rossjohn J, Ou H, Song J. Epitope-anchored contrastive transfer learning for paired CD8+ T cell receptor–antigen recognition. Nature Machine Intelligence 2024, 6: 1344-1358. DOI: 10.1038/s42256-024-00913-8.Peer-Reviewed Original ResearchPeptide-major histocompatibility complexT cellsEpitope-specific T cellsImmune responseResidue-level interactionsPredicted binding strengthSpike-specific immune responsesTCR-based immunotherapyTumor-associated antigensT cell antigen recognitionPredicted binding specificityAdaptive immune responsesTCR cross-reactivityTCR repertoireCross-reactivityBinding specificityAutoimmune diseasesImmunodominant epitopesContact residuesAntigen recognitionHistocompatibility complexTCRImmunotherapyDistance matrixT-cell receptor-antigen recognitionFOS+ B cells: Key mediators of immunotherapy resistance in diverse cancer types
Zhang X, Ma J, Chen Y, Deng X, Zhang Y, Han Y, Tan J, Deng G, Ouyang Y, Zhou Y, Cai C, Zeng S, Shen H. FOS+ B cells: Key mediators of immunotherapy resistance in diverse cancer types. Molecular Therapy Oncology 2024, 32: 200895. PMID: 39583007, PMCID: PMC11584611, DOI: 10.1016/j.omton.2024.200895.Peer-Reviewed Original ResearchImmunotherapy resistanceB cellsPoor response to immunotherapyExpression of Blimp-1Cancer typesResponse to immunotherapyDifferentiation of B cellsB cell subpopulationsAssociated with poor response to immunotherapyPredicting treatment responseAffecting treatment efficacyDiverse cancer typesImmunotherapy efficacyImmunotherapy patientsTumor microenvironmentTreatment responsePlasma cellsImmunotherapyImmunosuppressive effectsBlimp-1Spatial transcriptomic analysisTreatment efficacyOvercome resistanceCancer treatmentImmunofluorescence analysisThe hallmarks of cancer immune evasion
Galassi C, Chan T, Vitale I, Galluzzi L. The hallmarks of cancer immune evasion. Cancer Cell 2024, 42: 1825-1863. PMID: 39393356, DOI: 10.1016/j.ccell.2024.09.010.Peer-Reviewed Original ResearchCancer immune evasionHost immune systemImmune evasionNeoplastic cellsImmune systemImmune effector cellsConventional therapeutic strategiesModern immunotherapyAnticancer immunosurveillanceEffector cellsImmune escapeImmunoevasion mechanismsMalignant cellsMicroscopic neoplasmsCancer outgrowthImmune cytotoxicityImmune recognitionTherapeutic strategiesEpigenetic alterationsCancer cellsCell precursorsCancerCellsHallmarksImmunotherapyEP.07C.10 Real-World Outcomes of Patients Treated with Neoadjuvant Immunotherapy for Resectable Non-Small Cell Lung Cancer
Ermer T, Kim S, Goldberg S, Zolfaghari E, Blasberg J, Boffa D, Herbst R, Politi K, Schalper K, Dacic S, Woodard G. EP.07C.10 Real-World Outcomes of Patients Treated with Neoadjuvant Immunotherapy for Resectable Non-Small Cell Lung Cancer. Journal Of Thoracic Oncology 2024, 19: s543-s544. DOI: 10.1016/j.jtho.2024.09.1007.Peer-Reviewed Original ResearchWhat is the role of perioperative immunotherapy and chemotherapy in stage III resectable non-small cell lung cancer?
Zolfaghari E, Antonoff M. What is the role of perioperative immunotherapy and chemotherapy in stage III resectable non-small cell lung cancer? AME Clinical Trials Review 2024, 2: 73-73. DOI: 10.21037/actr-24-88.Peer-Reviewed Original ResearchEpigenetic control of immunoevasion in cancer stem cells
Galassi C, Esteller M, Vitale I, Galluzzi L. Epigenetic control of immunoevasion in cancer stem cells. Trends In Cancer 2024, 10: 1052-1071. PMID: 39244477, DOI: 10.1016/j.trecan.2024.08.004.Peer-Reviewed Original ResearchCancer stem cellsTumor-targeting immune responsesPopulation of malignant cellsStem cellsResistance to therapyStages of cancer progressionHost immune systemDisease relapseMalignant cellsTumor progressionImmune recognitionNeoplastic cellsImmune responseCancer progressionImmune systemEvade recognitionEpigenetic modification of DNATherapeutic targetCancerEpigenetic modificationsCellsEpigenetic controlModification of DNAImmunotherapyMalignancyDeciphering the HLA-E immunopeptidome with mass spectrometry: an opportunity for universal mRNA vaccines and T-cell-directed immunotherapies
Weitzen M, Shahbazy M, Kapoor S, Caron E. Deciphering the HLA-E immunopeptidome with mass spectrometry: an opportunity for universal mRNA vaccines and T-cell-directed immunotherapies. Frontiers In Immunology 2024, 15: 1442783. PMID: 39301027, PMCID: PMC11410602, DOI: 10.3389/fimmu.2024.1442783.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMass spectrometryHLA-EHLA moleculesT-cell-directed immunotherapyCD8+ T cellsNovel cell surface antigensNon-classical HLA-EHLA-E moleculesCell surface antigensPeptides to CD8T cellsMRNA vaccinesTherapeutic efficacySurface antigensImmunotherapyMoleculesSpectrometryTherapeutic targetImmunopeptidomePathogen-derivedCD8Peptide repertoirePeptide fragmentsHLAMinimal polymorphism
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