2025
Tumor microenvironment of non-small cell lung cancer impairs immune cell function among people with HIV
Desai S, Salahuddin S, Yusuf R, Ranjan K, Gu J, Osmani L, Lin Y, Mehta S, Talmon R, Kang I, Kluger Y, Zhao H, Schalper K, Emu B. Tumor microenvironment of non-small cell lung cancer impairs immune cell function among people with HIV. Journal Of Clinical Investigation 2025 PMID: 40459946, DOI: 10.1172/jci177310.Peer-Reviewed Original ResearchNon-small cell lung cancerTumor microenvironmentImmune cellsLung cancerCohort of non-small cell lung cancerExpression of PD-1Impairs anti-tumor responsesTumor-infiltrating CD8+Tumor-specific immune responsesCD4+ T cellsHIV-associated tumorsInfiltrating CD8+Expression of immunoregulatory moleculesAnti-tumor responsesTumor-associated macrophagesCell lung cancerImmune cell functionNSCLC cell linesPD-1Tumor killingBlocker therapyCD8+LAG-3Immune landscapeImmunoregulatory phenotypeA randomized phase 3 study of ivonescimab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of metastatic non–small cell lung cancer: HARMONi-3.
Zhang J, Cai J, Wang H, Yu Y, Bosch-Barrera J, Bernabé R, Andric Z, Badin F, Okuma Y, Paik P, Naidoo J, Kalofonos H, Wang B, Jotte R, Pennell N, Riess J, Doroshow D, Nishio M, Alatorre-Alexander J, Lu S. A randomized phase 3 study of ivonescimab plus chemotherapy versus pembrolizumab plus chemotherapy for the first-line treatment of metastatic non–small cell lung cancer: HARMONi-3. Journal Of Clinical Oncology 2025, 43 DOI: 10.1200/jco.2025.43.16_suppl.tps8664.Peer-Reviewed Original ResearchNon-small cell lung cancerProgression-free survivalFirst-line treatmentMetastatic non-small cell lung cancerCell lung cancerPD-1PD-L1Metastatic diseaseFirst-line treatment of metastatic non-small cell lung cancerLung cancerPD-L1 tumor proportion scoreTreatment of metastatic non-small cell lung cancerProgrammed cell death protein 1Cell death protein 1Programmed death-ligand 1Randomized phase 3 studyStandard first-line treatmentDevelopment of metastatic diseaseDisease control rateTumor proportion scoreDeath-ligand 1Platinum-doublet chemotherapyTargeting PD-1Duration of responseFirst-line therapyIL-4 mediated TAP2 downregulation is a dominant and reversible mechanism of immune evasion and immunotherapy resistance in non-small cell lung cancer
Ranjan K, Rajendran B, Deen I, Costantini A, de Rodas M, Desai S, Scallo F, Gianino N, Ferrone S, Schalper K. IL-4 mediated TAP2 downregulation is a dominant and reversible mechanism of immune evasion and immunotherapy resistance in non-small cell lung cancer. Molecular Cancer 2025, 24: 80. PMID: 40091029, PMCID: PMC11912681, DOI: 10.1186/s12943-025-02276-z.Peer-Reviewed Original ResearchThis study investigates IL-4's role in TAP2 downregulation as a reversible mechanism of immune evasion and resistance to immunotherapy in non-small cell lung cancer, highlighting potential therapeutic strategies to restore TAP2 expression and enhance treatment efficacy.Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases
Weiss S, Djureinovic D, Wei W, Tran T, Austin M, Markowitz J, Eroglu Z, Khushalani N, Hegde U, Cohen J, Sznol M, Anderson G, Johnson B, Piteo C, Mahajan A, Adeniran A, Jilaveanu L, Goldberg S, Chiang V, Forsyth P, Kluger H. Phase II Trial of Pembrolizumab in Combination With Bevacizumab for Untreated Melanoma Brain Metastases. Journal Of Clinical Oncology 2025, 43: 1685-1694. PMID: 40048689, PMCID: PMC12058415, DOI: 10.1200/jco-24-02219.Peer-Reviewed Original ResearchMelanoma brain metastasesOverall survivalBrain metastasesAnti-vascular endothelial growth factor therapyMedian intracranial progression-free survivalFour-year OS ratesIntracranial progression-free survivalResponse rateCirculating angiopoietin-2Median overall survivalTrial of pembrolizumabYears of pembrolizumabDose of bevacizumabProgression-free survivalPhase II trialGrowth factor therapyAdverse event ratesAssociated with responseOS ratesPD-1Radiation necrosisLocal therapyOn-therapyMetastatic tumorsFactor therapyPresence of Tertiary Lymphoid Structures and Exhausted Tissue-Resident T Cells Determines Clinical Response to PD-1 Blockade in Renal Cell Carcinoma.
Hugaboom M, Wirth L, Street K, Ruthen N, Jegede O, Schindler N, Shah V, Zaemes J, El Ahmar N, Matar S, Savla V, Choueiri T, Denize T, West D, McDermott D, Plimack E, Sosman J, Haas N, Stein M, Alter R, Bilen M, Hurwitz M, Hammers H, Signoretti S, Atkins M, Wu C, Braun D. Presence of Tertiary Lymphoid Structures and Exhausted Tissue-Resident T Cells Determines Clinical Response to PD-1 Blockade in Renal Cell Carcinoma. Cancer Discovery 2025, 15: 948-968. PMID: 39992403, PMCID: PMC12048281, DOI: 10.1158/2159-8290.cd-24-0991.Peer-Reviewed Original ResearchTertiary lymphoid structuresRenal cell carcinomaCD8+ T cellsAnti-PD1 monotherapyImmune checkpoint inhibitorsT cellsCell carcinomaLymphoid structuresClinical outcomesClinical response to PD-1 blockadeTreatment of advanced renal cell carcinomaResponse to PD-1 blockadePresence of tertiary lymphoid structuresAdvanced renal cell carcinomaTissue-resident T cellsPD-1 blockadePhase II clinical trialPD-1 pathwayCheckpoint inhibitorsICI resistancePD-1Responding patientsTumor microenvironmentTherapeutic responseTissue-residentPD-1H (VISTA) expression in cutaneous squamous cell carcinoma is correlated with T cell infiltration and activation
Kidacki M, Cho C, Lopez-Giraldez F, Huang B, He J, Gaule P, Chen L, Vesely M. PD-1H (VISTA) expression in cutaneous squamous cell carcinoma is correlated with T cell infiltration and activation. Journal Of Investigative Dermatology 2025 PMID: 39983979, DOI: 10.1016/j.jid.2025.01.030.Peer-Reviewed Original ResearchCutaneous squamous cell carcinomaPD-L1 expressionT cell infiltrationPD-L1Squamous cell carcinomaVISTA expressionPD-1HCell carcinomaT cellsBlockade of PD-1Proliferation marker Ki-67Multiplexed quantitative immunofluorescencePD-L1 coexpressionTreatment of cutaneous squamous cell carcinomaControl T cellsPreclinical cancer studiesMyeloid cell functionImmunosuppressive microenvironmentPD-1Receptor antagonismKi-67Individual tumorsGranzyme B.Clinical trialsCancer clinical trialsINTerpath-004: A phase 2, randomized, double-blind study of adjuvant pembrolizumab (pembro) with V940 (mRNA-4157) or placebo for renal cell carcinoma (RCC).
Motzer R, Braun D, Powles T, Gurney H, Fong L, George D, Haas N, McDermott D, Shuch B, Meehan R, Posadas T, Wu S, Elfiky A, Choueiri T. INTerpath-004: A phase 2, randomized, double-blind study of adjuvant pembrolizumab (pembro) with V940 (mRNA-4157) or placebo for renal cell carcinoma (RCC). Journal Of Clinical Oncology 2025, 43: tps610-tps610. DOI: 10.1200/jco.2025.43.5_suppl.tps610.Peer-Reviewed Original ResearchRenal cell carcinomaWeeks prior to randomizationAdverse eventsTumor-specific T-cell activationResection of metastatic lesionsAdjuvant treatment of patientsIncreased risk of recurrenceStage III/IV melanomaImmune checkpoint inhibitorsDisease-free survivalMetastasis-free survivalPhase 2 trialRisk of recurrenceDouble-blind studyT cell activationTreatment of patientsNovel combination strategiesDose of treatmentAdjuvant pembrolizumabAdjuvant settingCheckpoint inhibitorsPapillary histologyPD-1Sarcomatoid featuresMetastatic lesionsAssociation between PD-1 expression on tumor-infiltrating regulatory T cells and resistance to first-line nivolumab in advanced clear cell renal cell carcinoma: Insights from the HCRN GU16-260 clinical trial.
Mohanna R, Simsek B, El Ahmar N, Jegede O, Matar S, Paul M, Nabil Laimon Y, Roberti De Oliveira G, Delcea A, Choueiri T, Braun D, Haas N, Hammers H, Bilen M, Stein M, Sosman J, Wu C, McDermott D, Atkins M, Signoretti S. Association between PD-1 expression on tumor-infiltrating regulatory T cells and resistance to first-line nivolumab in advanced clear cell renal cell carcinoma: Insights from the HCRN GU16-260 clinical trial. Journal Of Clinical Oncology 2025, 43: 590-590. DOI: 10.1200/jco.2025.43.5_suppl.590.Peer-Reviewed Original ResearchAdvanced clear cell renal cell carcinomaClear cell renal cell carcinomaProgression-free survivalPD-1 expressionTumor-infiltrating TregsCell renal cell carcinomaRegulatory T cellsPD-1Renal cell carcinomaClinical trialsCell carcinomaT cellsEfficacy of PD-1 blockadeInhibition of PD-1 signalingLevel of PD-1 expressionShorter median progression-free survivalTumor-infiltrating regulatory T cellsAssociated with progression-free survivalMedian progression-free survivalPercentage of PD-1First-line nivolumabFirst-line settingPD-1 blockadePD-1 signalingLog-rank testNanrilkefusp alfa (SOT101), an IL-15 receptor βγ superagonist, as a single agent or with anti-PD-1 in patients with advanced cancers
Champiat S, Garralda E, Galvao V, Cassier P, Gomez-Roca C, Korakis I, Grell P, Naing A, LoRusso P, Mikyskova R, Podzimkova N, Reinis M, Ouali K, Schoenenberger A, Kiemle-Kallee J, Tillmanns S, Sachse R, Moebius U, Spisek R, Bechard D, Jelinkova L, Adkins I, Marabelle A. Nanrilkefusp alfa (SOT101), an IL-15 receptor βγ superagonist, as a single agent or with anti-PD-1 in patients with advanced cancers. Cell Reports Medicine 2025, 6: 101967. PMID: 39933529, PMCID: PMC11866505, DOI: 10.1016/j.xcrm.2025.101967.Peer-Reviewed Original ResearchConceptsCD8<sup>+</sup> T cellsNatural killerT cellsAnti-programmed cell death protein 1Frequent treatment-emergent adverse eventsProportion of CD8<sup>+</sup> T cellsAnti-PD-1 pembrolizumabTreatment-emergent adverse eventsCell death protein 1Anti-PD-1Advanced/metastatic solid tumorsStimulated natural killerInjection site reactionsIL-15 receptorMouse tumor modelsPD-1NK cellsPeripheral bloodIL-15Safety profileSite reactionsSolid tumorsClinical efficacyAdverse eventsTumor modelPhase 1 trial of hypofractionated stereotactic re-irradiation in combination with nivolumab, ipilimumab, and bevacizumab for recurrent high-grade gliomas
Sahebjam S, Raval R, Forsyth P, Enderling H, Tran N, Arrington J, Macaulay R, Perlow H, Palmer J, Ghose J, Rajappa P, Giglio P, Li Z, Etame A, Mokhtari S, Cruz-Chamorro R, Bhandari M, Thapa R, Robinson T, Chen D, Yu H. Phase 1 trial of hypofractionated stereotactic re-irradiation in combination with nivolumab, ipilimumab, and bevacizumab for recurrent high-grade gliomas. Neuro-Oncology Advances 2025, 7: vdaf033. PMID: 40134851, PMCID: PMC11934552, DOI: 10.1093/noajnl/vdaf033.Peer-Reviewed Original ResearchTreatment-related adverse eventsStereotactic re-irradiationRecurrent high-grade gliomaHigh-grade gliomasRe-IrradiationPD-1PD-1 blockadeProgression-free survivalPhase I studySecondary end pointsPhase 1 trialRecurrent HGGCheckpoint immunotherapyOverall survivalRecurrent glioblastomaAnaplastic astrocytomaBevacizumabNivolumabIpilimumabGrade 3Adverse eventsClinical investigationImmune responseEnd pointsPatientsFamitinib plus camrelizumab in patients with advanced colorectal cancer: Data from a multicenter, basket study
Ai L, Li Q, Zhang S, Dong Y, Yang M, Li J, Pan Y, Yuan Y, Yi S, Wang J, Cheng Y, Feng J, Gao S, Wang X, Qu S, Zhang X, Lu J, Xiu P, Wang S, Yang X, Yu Y, Liu T. Famitinib plus camrelizumab in patients with advanced colorectal cancer: Data from a multicenter, basket study. The Innovation 2025, 6: 100745. PMID: 39872476, PMCID: PMC11763884, DOI: 10.1016/j.xinn.2024.100745.Peer-Reviewed Original ResearchProgression-free survivalDuration of responseAdvanced colorectal cancerOverall survivalColorectal cancerMedian duration of responseMedian progression-free survivalMetastatic colorectal cancer patientsTreatment-related adverse eventsMedian follow-up timeMedian overall survivalMetastatic solid tumorsPD-1 antagonistsFollow-up timeCohort of patientsAnti-angiogenic agentsColorectal cancer patientsInhibition of angiogenesisPD-1Immune checkpointsMetastatic diseaseBasket studyMedian durationPrimary endpointSystemic treatment
2024
Impact of radiation therapy dose, fractionation, and immunotherapeutic partner in a mouse model of hormone receptor–positive mammary carcinogenesis
Buqué A, Bloy N, Petroni G, Jiménez-Cortegana C, Sato A, Iribarren C, Yamazaki T, Galassi C, Hensler M, Bhinder B, Guarracino A, Rippon B, Beltran-Visiedo M, Soler-Agesta R, Pannellini T, Fucikova J, Demaria S, Zhou X, Elemento O, Formenti S, Galluzzi L. Impact of radiation therapy dose, fractionation, and immunotherapeutic partner in a mouse model of hormone receptor–positive mammary carcinogenesis. Journal Of The National Cancer Institute 2024, 117: 934-947. PMID: 39661487, PMCID: PMC12058254, DOI: 10.1093/jnci/djae329.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsRadiation therapyFocal RTOverall survivalMammary carcinogenesisPD-1Impact of radiotherapy doseMouse modelPD-1 blockerRT plus immunotherapyPrimary tumor growthPrimary disease controlIncrease local controlCheckpoint inhibitorsRadiotherapy doseHypofractionated RTOS benefitTumor burdenPrimary tumorBreast cancerTumor growthNeoplastic lesionsLocal controlICI sensitivityEffective immunityGold-siRNA supraclusters enhance the anti-tumor immune response of stereotactic ablative radiotherapy at primary and metastatic tumors
Jiang Y, Cao H, Deng H, Guan L, Langthasa J, Colburg D, Melemenidis S, Cotton R, Aleman J, Wang X, Graves E, Kalbasi A, Pu K, Rao J, Le Q. Gold-siRNA supraclusters enhance the anti-tumor immune response of stereotactic ablative radiotherapy at primary and metastatic tumors. Nature Biotechnology 2024, 1-14. PMID: 39448881, PMCID: PMC12018592, DOI: 10.1038/s41587-024-02448-0.Peer-Reviewed Original ResearchStereotactic ablative radiotherapyAnti-tumor immune responseSmall interfering RNAAblative radiotherapyMetastatic tumorsEffect of stereotactic ablative radiotherapyModel of head and neck cancerHead and neck cancerImmunosuppressive cell populationsPD-1 inhibitorsSmall interfering RNA complexesPD-1Primary tumorImmunotherapeutic effectsNeck cancerGranzyme BGal-1Mouse modelPassive deliveryTumorReduced toxicityCell populationsRadiotherapyRadiosensitivityRenal filtration thresholdNivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial
Wu J, Zhang S, Yu S, An G, Wang Y, Yu Y, Liang L, Wang Y, Xu X, Xiong Y, Shao D, Shi Z, Li N, Wang J, Jin D, Liu T, Cui Y. Nivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial. Nature Communications 2024, 15: 8876. PMID: 39406730, PMCID: PMC11480398, DOI: 10.1038/s41467-024-53109-4.Peer-Reviewed Original ResearchConceptsEsophageal squamous cell carcinomaAdvanced gastric adenocarcinomaSquamous cell carcinomaTyrosine kinase inhibitorsGastric adenocarcinomaVariant allele frequencyAnlotinib hydrochlorideCell carcinomaVascular endothelial growth factor inhibitorsAnti-PD-1 antibodySafety of nivolumabAnti-PD-1Disease control rateMedian overall survivalProgression-free survivalGrowth factor inhibitorsPhase II trialOverall response rateOASIS trialPD-1Second-lineOverall survivalImmune signaturesII trialFactor inhibitorsTIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3
Perales O, Jilaveanu L, Adeniran A, Su D, Hurwitz M, Braun D, Kluger H, Schoenfeld D. TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3. Cancer Immunology, Immunotherapy 2024, 73: 192. PMID: 39105820, PMCID: PMC11303630, DOI: 10.1007/s00262-024-03773-8.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaRenal cell carcinoma tumorsT cellsTIGIT expressionCheckpoint inhibitorsPD-1Likelihood of response to therapyTumor-infiltrating T cellsCD3+ T cellsRenal cell carcinoma metastasisTreatment of renal cell carcinomaImmune checkpoint inhibitorsInfiltrating T cellsPurposeImmune checkpoint inhibitorsResponse to therapyT cell immunoglobulinCD3+ levelsMetastatic RCC specimensAdjacent normal renal tissuesNormal renal tissuesQuantitative immunofluorescence analysisCell carcinomaResistant diseasePotential therapeutic targetTissue microarrayPatterns of brain metastases response to immunotherapy with pembrolizumab
Mahajan A, Goldberg S, Weiss S, Tran T, Singh K, Joshi K, Aboian M, Kluger H, Chiang V. Patterns of brain metastases response to immunotherapy with pembrolizumab. Journal Of Neuro-Oncology 2024, 169: 555-561. PMID: 38963658, DOI: 10.1007/s11060-024-04754-8.Peer-Reviewed Original ResearchNon-small cell lung cancerBrain metastasesComplete resolutionLung cancerMedian time to CNS progressionLesion progressionNon-small cell lung cancer patientsModified RECIST criteriaPD-1 inhibitorsTrial of pembrolizumabEffective systemic treatmentResponse to immunotherapyPhase II trialCell lung cancerMethodsThis retrospective studyLocal treatment decisionsPurposeCentral nervous systemCNS progressionRECIST criteriaPD-1Local therapySystemic treatmentMRI evaluationResponse assessmentRetrospective studyObesity induces PD-1 on macrophages to suppress anti-tumour immunity
Bader J, Wolf M, Lupica-Tondo G, Madden M, Reinfeld B, Arner E, Hathaway E, Steiner K, Needle G, Hatem Z, Landis M, Faneuff E, Blackman A, Wolf E, Cottam M, Ye X, Bates M, Smart K, Wang W, Pinheiro L, Christofides A, Smith D, Boussiotis V, Haake S, Beckermann K, Wellen K, Reinhart-King C, Serezani C, Lee C, Aubrey C, Chen H, Rathmell W, Hasty A, Rathmell J. Obesity induces PD-1 on macrophages to suppress anti-tumour immunity. Nature 2024, 630: 968-975. PMID: 38867043, PMCID: PMC11456854, DOI: 10.1038/s41586-024-07529-3.Peer-Reviewed Original ResearchTumor-associated macrophagesPD-1 expressionInduced PD-1 expressionPD-1T cellsIncreased CD8+ T cell activationCD8+ T cell activationResponse to immune checkpoint blockade therapyT-cell stimulatory potentialTumor-associated macrophage expressionSuppress anti-tumor immunityImmune checkpoint blockade therapyObesity-cancer connectionPD-1 deficiencyAnti-PD-1PD-1 blockadePD-1 inhibitionAnti-tumor immunityCheckpoint blockade therapyTargeting PD-1Tumor immune surveillancePD-1 immunotherapyAntigen presentation capabilityMarkers of exhaustionExpression of CD86Serine Depletion Promotes Antitumor Immunity by Activating Mitochondrial DNA-Mediated cGAS-STING Signaling.
Saha S, Ghosh M, Li J, Wen A, Galluzzi L, Martinez L, Montrose D. Serine Depletion Promotes Antitumor Immunity by Activating Mitochondrial DNA-Mediated cGAS-STING Signaling. Cancer Research 2024, 84: 2645-2659. PMID: 38861367, PMCID: PMC11326969, DOI: 10.1158/0008-5472.can-23-1788.Peer-Reviewed Original ResearchAnti-tumor immunityImmune checkpoint inhibitors targeting PD-1Improved response to immune checkpoint inhibitorsCheckpoint inhibitors targeting PD-1Infiltration of immune effector cellsSuppressors of anti-tumor immunityColorectal cancerResponse to immune checkpoint inhibitorsEnhance tumor immunogenicityI interferonImmune checkpoint inhibitorsT-cell depletionCancer metabolismSerine deprivationImmune effector cellsSensitivity of tumorsType I IFN signalingAnti-neoplastic effectsImmune-enhancing effectsDisrupted metabolic pathwaysColorectal cancer cellsType I interferonCheckpoint inhibitorsIntratumoral infiltrationPD-1Emerging Novel Functional Imaging and Immunotherapy in Renal Cell Carcinoma and Current Treatment Sequencing Strategies After Immunotherapy.
Ali M, Eid M, Saliby R, Choi S, McKay R, Siva S, Braun D, Chen Y. Emerging Novel Functional Imaging and Immunotherapy in Renal Cell Carcinoma and Current Treatment Sequencing Strategies After Immunotherapy. American Society Of Clinical Oncology Educational Book 2024, 44: e438658. PMID: 38875505, DOI: 10.1200/edbk_438658.Peer-Reviewed Original ResearchConceptsRenal cell carcinomaTreatment sequencing strategiesCell carcinomaImmune checkpoint inhibitors targeting PD-1Chimeric antigen receptor T-cell therapyCheckpoint inhibitors targeting PD-1Management of renal cell carcinomaAdvanced renal cell carcinomaProstate-specific membrane antigenLandscape of renal cell carcinomaRCC-associated antigensImmune checkpoint inhibitionT-cell therapyPrimary kidney tumorsAssess treatment responseChanging treatment landscapeCarbonic anhydrase IXFunctional imagingFunctional imaging modalitiesCheckpoint inhibitionPD-1Immunotherapy strategiesLAG-3Membrane antigenT cellsState-of-the-Art Advancements in Gastroesophageal Cancer Treatment: Harnessing Biomarkers for Precision Care.
Balmaceda N, Petrillo A, Krishnan M, Zhao J, Kim S, Klute K, Sundar R. State-of-the-Art Advancements in Gastroesophageal Cancer Treatment: Harnessing Biomarkers for Precision Care. American Society Of Clinical Oncology Educational Book 2024, 44: e431060. PMID: 38771996, DOI: 10.1200/edbk_431060.Peer-Reviewed Original ResearchConceptsGastroesophageal cancerIntegration of immune checkpoint inhibitorsChimeric antigen receptor T cellsImmune checkpoint inhibitorsMetastatic gastroesophageal cancerPD-1 inhibitorsAdoptive cell therapyImmunotherapy-based approachesResectable gastroesophageal cancerAntibody-drug conjugatesCheckpoint inhibitorsPD-1Perioperative chemotherapyTargeted therapyT cellsTreatment paradigmFGFR2 inhibitorsCell therapyClinical challengeBispecific antibodiesImprove outcomesCancer treatmentReduced toxicityTherapyInhibitors
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