2023
Spatial characterization and quantification of CD40 expression across cancer types
Bates K, Vathiotis I, MacNeil T, Ahmed F, Aung T, Katlinskaya Y, Bhattacharya S, Psyrri A, Yea S, Parkes A, Sadraei N, Roychoudhury S, Rimm D, Gavrielatou N. Spatial characterization and quantification of CD40 expression across cancer types. BMC Cancer 2023, 23: 220. PMID: 36894898, PMCID: PMC9996913, DOI: 10.1186/s12885-023-10650-7.Peer-Reviewed Original ResearchConceptsCD40 expressionSolid tumorsTumor cellsQuantitative immunofluorescencePatient cohortPancreatic cancerCancer typesExpression of CD40Large patient cohortOvarian cancer populationTissue microarray formatDifferent solid tumorsInnate immune responseTNF receptor family membersAvailable patient cohortNSCLC populationOverall survivalPrognostic impactReceptor family membersCancer populationAdenocarcinoma populationImmune cellsOvarian cancerPancreatic adenocarcinomaPositivity rate
2021
PD-L1 as a biomarker of response to immune-checkpoint inhibitors
Doroshow DB, Bhalla S, Beasley MB, Sholl LM, Kerr KM, Gnjatic S, Wistuba II, Rimm DL, Tsao MS, Hirsch FR. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nature Reviews Clinical Oncology 2021, 18: 345-362. PMID: 33580222, DOI: 10.1038/s41571-021-00473-5.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsSelection of patientsPD-L1L1 antibodyImmunohistochemistry assaysPD-L1 immunohistochemistry assaysOutcomes of patientsBiomarkers of responseCompanion diagnostic assayTypes of cancerPD-1Clinical outcomesSelection biomarkerProspective comparisonClinical challengeNew therapiesFuture treatmentPatientsSolid tumorsClinical useSpecific agentsInter-assay variabilityBiomarkersCurrent roleDiagnostic assays
2020
Trial in progress: A phase I/II, open-label, dose-escalation, safety and tolerability study of NC318 in subjects with advanced or metastatic solid tumors.
Gutierrez M, Hamid O, Shum E, Wise D, Balar A, Weber J, LoRusso P, Shafi S, Rimm D, Tolcher A, Basudhar D, Dujka M, Heller K. Trial in progress: A phase I/II, open-label, dose-escalation, safety and tolerability study of NC318 in subjects with advanced or metastatic solid tumors. Journal Of Clinical Oncology 2020, 38: tps3166-tps3166. DOI: 10.1200/jco.2020.38.15_suppl.tps3166.Peer-Reviewed Original ResearchMetastatic solid tumorsT cell functionSolid tumorsPD-L1 tumor proportion scoreAnti-tumor immune responseNon-small cell lungPhase I/IIPhase 2 doseTumor proportion scoreAnti-tumor immunityKey eligibility criteriaCell functionDose-escalation designBreast cancer subjectsNon-randomized studiesT cell proliferationPrevents tumor growthClass monoclonal antibodyCollection of biopsiesMeasurable diseaseRECIST v1.1Phase 1/2Escalation designTolerability studyImmune suppressionReport on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group
Amgad M, Stovgaard ES, Balslev E, Thagaard J, Chen W, Dudgeon S, Sharma A, Kerner JK, Denkert C, Yuan Y, AbdulJabbar K, Wienert S, Savas P, Voorwerk L, Beck AH, Madabhushi A, Hartman J, Sebastian MM, Horlings HM, Hudeček J, Ciompi F, Moore DA, Singh R, Roblin E, Balancin ML, Mathieu MC, Lennerz JK, Kirtani P, Chen IC, Braybrooke JP, Pruneri G, Demaria S, Adams S, Schnitt SJ, Lakhani SR, Rojo F, Comerma L, Badve SS, Khojasteh M, Symmans WF, Sotiriou C, Gonzalez-Ericsson P, Pogue-Geile KL, Kim RS, Rimm DL, Viale G, Hewitt SM, Bartlett JMS, Penault-Llorca F, Goel S, Lien HC, Loibl S, Kos Z, Loi S, Hanna MG, Michiels S, Kok M, Nielsen TO, Lazar AJ, Bago-Horvath Z, Kooreman LFS, van der Laak JAWM, Saltz J, Gallas BD, Kurkure U, Barnes M, Salgado R, Cooper LAD. Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group. Npj Breast Cancer 2020, 6: 16. PMID: 32411818, PMCID: PMC7217824, DOI: 10.1038/s41523-020-0154-2.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesComputer-aided diagnosticsPotential of machineAssessment of algorithmsInternational Immuno-Oncology Biomarker Working GroupHER2-positive breast cancerBiomarker Working GroupComputational workflowPrognostic workflowsVisual guidelinesTIL assessmentInfiltrating lymphocytesBreast cancerPredictive featuresSolid tumorsInter-reader variabilityWorkflowClinical validationComputational assessmentRipe opportunityComputational methodsReporting guidelinesLymphocytesVisual scoringClinical translation
2019
Suppressing miR-21 activity in tumor-associated macrophages promotes an antitumor immune response
Sahraei M, Chaube B, Liu Y, Sun J, Kaplan A, Price NL, Ding W, Oyaghire S, García-Milian R, Mehta S, Reshetnyak YK, Bahal R, Fiorina P, Glazer PM, Rimm DL, Fernández-Hernando C, Suárez Y. Suppressing miR-21 activity in tumor-associated macrophages promotes an antitumor immune response. Journal Of Clinical Investigation 2019, 129: 5518-5536. PMID: 31710308, PMCID: PMC6877327, DOI: 10.1172/jci127125.Peer-Reviewed Original ResearchConceptsTumor-associated macrophagesMiR-21 expressionTumor growthMiR-21Immune responseCytotoxic T cell responsesC motif chemokine 10Antitumor immune responseT cell responsesAntitumoral immune responseTumor immune infiltratesInduction of cytokinesPotential therapeutic implicationsMiR-21 inhibitionStages of carcinogenesisAngiostatic phenotypeTumor cell deathIL-12Immune infiltratesTherapeutic implicationsSolid tumorsTumor neovascularizationTumor progressionTumor microenvironmentTumor pathogenesis
2017
Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors
Hendry S, Salgado R, Gevaert T, Russell PA, John T, Thapa B, Christie M, van de Vijver K, Estrada MV, Gonzalez-Ericsson PI, Sanders M, Solomon B, Solinas C, Van den Eynden GGGM, Allory Y, Preusser M, Hainfellner J, Pruneri G, Vingiani A, Demaria S, Symmans F, Nuciforo P, Comerma L, Thompson EA, Lakhani S, Kim SR, Schnitt S, Colpaert C, Sotiriou C, Scherer SJ, Ignatiadis M, Badve S, Pierce RH, Viale G, Sirtaine N, Penault-Llorca F, Sugie T, Fineberg S, Paik S, Srinivasan A, Richardson A, Wang Y, Chmielik E, Brock J, Johnson DB, Balko J, Wienert S, Bossuyt V, Michiels S, Ternes N, Burchardi N, Luen SJ, Savas P, Klauschen F, Watson PH, Nelson BH, Criscitiello C, O’Toole S, Larsimont D, de Wind R, Curigliano G, André F, Lacroix-Triki M, van de Vijver M, Rojo F, Floris G, Bedri S, Sparano J, Rimm D, Nielsen T, Kos Z, Hewitt S, Singh B, Farshid G, Loibl S, Allison KH, Tung N, Adams S, Willard-Gallo K, Horlings HM, Gandhi L, Moreira A, Hirsch F, Dieci MV, Urbanowicz M, Brcic I, Korski K, Gaire F, Koeppen H, Lo A, Giltnane J, Rebelatto MC, Steele KE, Zha J, Emancipator K, Juco JW, Denkert C, Reis-Filho J, Loi S, Fox SB. Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors. Advances In Anatomic Pathology 2017, 24: 311-335. PMID: 28777143, PMCID: PMC5638696, DOI: 10.1097/pap.0000000000000161.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBiopsyBrain NeoplasmsCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellEndometrial NeoplasmsFemaleGastrointestinal NeoplasmsHead and Neck NeoplasmsHumansImmunohistochemistryLung NeoplasmsLymphocytes, Tumor-InfiltratingMelanomaMesotheliomaOvarian NeoplasmsPathologyPhenotypePredictive Value of TestsSkin NeoplasmsSquamous Cell Carcinoma of Head and NeckUrogenital NeoplasmsConceptsTumor-infiltrating lymphocytesDifferent tumor typesSolid tumorsTumor typesTIL assessmentImmune responsePrimary brain tumorsCommon solid tumorsInvasive breast carcinomaRoutine clinical biomarkersWorking Group guidelinesPrognostic implicationsBreast carcinomaGroup guidelinesGynecologic systemGastrointestinal tractSimple biomarkerBrain tumorsGenitourinary systemPredictive valueClinical biomarkersStandardized methodologyTumorsAvailable evidenceImmunotherapyAssessing Tumor-infiltrating Lymphocytes in Solid Tumors
Hendry S, Salgado R, Gevaert T, Russell PA, John T, Thapa B, Christie M, van de Vijver K, Estrada MV, Gonzalez-Ericsson PI, Sanders M, Solomon B, Solinas C, Van den Eynden GGGM, Allory Y, Preusser M, Hainfellner J, Pruneri G, Vingiani A, Demaria S, Symmans F, Nuciforo P, Comerma L, Thompson EA, Lakhani S, Kim SR, Schnitt S, Colpaert C, Sotiriou C, Scherer SJ, Ignatiadis M, Badve S, Pierce RH, Viale G, Sirtaine N, Penault-Llorca F, Sugie T, Fineberg S, Paik S, Srinivasan A, Richardson A, Wang Y, Chmielik E, Brock J, Johnson DB, Balko J, Wienert S, Bossuyt V, Michiels S, Ternes N, Burchardi N, Luen SJ, Savas P, Klauschen F, Watson PH, Nelson BH, Criscitiello C, O’Toole S, Larsimont D, de Wind R, Curigliano G, André F, Lacroix-Triki M, van de Vijver M, Rojo F, Floris G, Bedri S, Sparano J, Rimm D, Nielsen T, Kos Z, Hewitt S, Singh B, Farshid G, Loibl S, Allison KH, Tung N, Adams S, Willard-Gallo K, Horlings HM, Gandhi L, Moreira A, Hirsch F, Dieci MV, Urbanowicz M, Brcic I, Korski K, Gaire F, Koeppen H, Lo A, Giltnane J, Rebelatto MC, Steele KE, Zha J, Emancipator K, Juco JW, Denkert C, Reis-Filho J, Loi S, Fox SB. Assessing Tumor-infiltrating Lymphocytes in Solid Tumors. Advances In Anatomic Pathology 2017, 24: 235-251. PMID: 28777142, PMCID: PMC5564448, DOI: 10.1097/pap.0000000000000162.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesTIL assessmentInvasive breast carcinomaSolid tumor typesBreast carcinomaSolid tumorsTumor typesDifferent solid tumor typesForm of immunotherapyImmune checkpoint inhibitorsEra of immunotherapyImportant prognostic informationRoutine clinical biomarkersHost immune responseWorking Group guidelinesDiverse solid tumor typesCheckpoint inhibitorsMetastatic settingPrognostic informationGroup guidelinesImmune responseEosin sectionsHistopathologic specimensClinical validityPredictive significanceErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC
Alvarado D, Ligon GF, Lillquist JS, Seibel SB, Wallweber G, Neumeister VM, Rimm DL, McMahon G, LaVallee TM. ErbB activation signatures as potential biomarkers for anti-ErbB3 treatment in HNSCC. PLOS ONE 2017, 12: e0181356. PMID: 28723928, PMCID: PMC5517012, DOI: 10.1371/journal.pone.0181356.Peer-Reviewed Original ResearchConceptsNeuregulin-1NRG1 expressionErbB3 activationNeck squamous cell carcinomaSquamous cell carcinomaEnhanced anti-tumor activitySubset of HNSCCUnmet medical needHNSCC cell linesHNSCC patient samplesAnti-tumor activityGrowth factor αLigand neuregulin-1Cell carcinomaEGFR/ErbB familyHNSCC modelsCetuximab treatmentErbB receptor inhibitionReceptor inhibitionReceptor levelsRespective signaling pathwaysSolid tumorsTumor typesHNSCCPotential biomarkers