2024
CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors
Skoulidis F, Araujo H, Do M, Qian Y, Sun X, Cobo A, Le J, Montesion M, Palmer R, Jahchan N, Juan J, Min C, Yu Y, Pan X, Arbour K, Vokes N, Schmidt S, Molkentine D, Owen D, Memmott R, Patil P, Marmarelis M, Awad M, Murray J, Hellyer J, Gainor J, Dimou A, Bestvina C, Shu C, Riess J, Blakely C, Pecot C, Mezquita L, Tabbó F, Scheffler M, Digumarthy S, Mooradian M, Sacher A, Lau S, Saltos A, Rotow J, Johnson R, Liu C, Stewart T, Goldberg S, Killam J, Walther Z, Schalper K, Davies K, Woodcock M, Anagnostou V, Marrone K, Forde P, Ricciuti B, Venkatraman D, Van Allen E, Cummings A, Goldman J, Shaish H, Kier M, Katz S, Aggarwal C, Ni Y, Azok J, Segal J, Ritterhouse L, Neal J, Lacroix L, Elamin Y, Negrao M, Le X, Lam V, Lewis W, Kemp H, Carter B, Roth J, Swisher S, Lee R, Zhou T, Poteete A, Kong Y, Takehara T, Paula A, Parra Cuentas E, Behrens C, Wistuba I, Zhang J, Blumenschein G, Gay C, Byers L, Gibbons D, Tsao A, Lee J, Bivona T, Camidge D, Gray J, Lieghl N, Levy B, Brahmer J, Garassino M, Gandara D, Garon E, Rizvi N, Scagliotti G, Wolf J, Planchard D, Besse B, Herbst R, Wakelee H, Pennell N, Shaw A, Jänne P, Carbone D, Hellmann M, Rudin C, Albacker L, Mann H, Zhu Z, Lai Z, Stewart R, Peters S, Johnson M, Wong K, Huang A, Winslow M, Rosen M, Winters I, Papadimitrakopoulou V, Cascone T, Jewsbury P, Heymach J. CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors. Nature 2024, 635: 462-471. PMID: 39385035, PMCID: PMC11560846, DOI: 10.1038/s41586-024-07943-7.Peer-Reviewed Original ResearchNon-small-cell lung cancerImmune checkpoint blockadeTumor suppressor genePD-L1Advanced non-small-cell lung cancerCD8+ cytotoxic T cellsSuppressor geneCD4+ effector cellsDual immune checkpoint blockadeMouse modelPD-L1 inhibitor durvalumabSuppressive myeloid cellsPD-L1 inhibitorsImmune-related toxicitiesPD-(L)1 inhibitorsAnti-tumor efficacyCytotoxic T cellsMyeloid cell compartmentAdverse tumor microenvironmentAssociated with higher ratesAnti-tumor activityLoss of Keap1CTLA4 inhibitorsSTK11 alterationsCheckpoint blockade
2023
The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion
Globig A, Zhao S, Roginsky J, Maltez V, Guiza J, Avina-Ochoa N, Heeg M, Araujo Hoffmann F, Chaudhary O, Wang J, Senturk G, Chen D, O’Connor C, Pfaff S, Germain R, Schalper K, Emu B, Kaech S. The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion. Nature 2023, 622: 383-392. PMID: 37731001, PMCID: PMC10871066, DOI: 10.1038/s41586-023-06568-6.Peer-Reviewed Original ResearchConceptsImmune checkpoint blockadeCell exhaustionExhausted CD8Sympathetic nervesT cell exhaustionSympathetic stress responsePancreatic cancer modelAnti-tumor functionCheckpoint blockadeCatecholamine levelsTissue innervationCytokine productionChronic antigenMalignant diseaseChronic infectionCD8Immune responseAdrenergic signalingEffector functionsΒ-blockersViral infectionCancer modelExhausted stateCell responsesCell function
2021
240 Discovery of biomarkers of resistance to immune checkpoint blockade in non-small-cell lung cancer (NSCLC) using high-plex digital spatial profiling
Moutafi M, Martinez-Morilla S, Divakar P, Vathiotis I, Gavrielatou N, Aung T, Yaghoobi V, Fernandez A, Fraile J, Schalper K, Rimm D. 240 Discovery of biomarkers of resistance to immune checkpoint blockade in non-small-cell lung cancer (NSCLC) using high-plex digital spatial profiling. 2021, a258-a258. DOI: 10.1136/jitc-2021-sitc2021.240.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsPre-treatment samplesQuantitative immunofluorescencePredictive biomarkersLung cancerHigh PD-L1 expressionExpression of CD66bInitial biomarker discoveryOperable NSCLC patientsStromal immune cellsTwo-sided significance levelPD-L1 expressionImmune checkpoint blockadeRole of neutrophilsCell lung cancerPotential predictive biomarkersGood predictive valueDigital spatial profilingDigital Spatial ProfilerCohort validationICI therapyCheckpoint inhibitorsCheckpoint blockadeNSCLC cohortNSCLC patients
2020
Trial in progress: A phase II open-label, randomized study of PARP inhibition (olaparib) either alone or in combination with anti-PD-L1 therapy (atezolizumab) in homologous DNA repair (HDR) deficient, locally advanced or metastatic non-HER2-positive breast cancer.
LoRusso P, Pilat M, Santa-Maria C, Connolly R, Roesch E, Afghahi A, Han H, Nanda R, Wulf G, Assad H, Park H, Dees E, Force J, Noonan A, Brufsky A, Abramson V, Haley B, Buys S, Sharon E, Schalper K. Trial in progress: A phase II open-label, randomized study of PARP inhibition (olaparib) either alone or in combination with anti-PD-L1 therapy (atezolizumab) in homologous DNA repair (HDR) deficient, locally advanced or metastatic non-HER2-positive breast cancer. Journal Of Clinical Oncology 2020, 38: tps1102-tps1102. DOI: 10.1200/jco.2020.38.15_suppl.tps1102.Peer-Reviewed Original ResearchPositive breast cancerPo bidPARP inhibitionBreast cancerImmune responseOpen-label phase II clinical trialAdaptive anti-tumor immune responsesAnti-tumor immune responsePhase II clinical trialMarked lymphocyte infiltrationPD-1 blockadePD-L1 expressionPre-treatment biopsiesProgression-free survivalAntitumor immune responseImmune checkpoint blockadeMajority of patientsBRCA 1/2 mutationsTumor immune contextureBiopsy time pointsHomologous DNA repairPARP inhibitor olaparibMonotherapy armCombination armImmune contexture
2016
Basic Overview of Current Immunotherapy Approaches in Cancer
Velcheti V, Schalper K. Basic Overview of Current Immunotherapy Approaches in Cancer. American Society Of Clinical Oncology Educational Book 2016, 35: 298-308. PMID: 27249709, DOI: 10.1200/edbk_156572.Peer-Reviewed Original ResearchConceptsHost-tumor immune interactionsCurrent immunotherapy approachesPromising new therapeutic strategyRole of immunotherapyImmune checkpoint blockadeHost-tumor interactionsNew therapeutic strategiesCheckpoint blockadeImmunotherapy strategiesImmunotherapy approachesTreatment of cancerCombinatorial immunotherapyImmune interactionsTherapeutic strategiesImmune evasionImmunotherapyCancerMultiple mechanismsMalignancyBlockade