2022
Role of tumor infiltrating lymphocytes and spatial immune heterogeneity in sensitivity to PD-1 axis blockers in non-small cell lung cancer
de Rodas M, Nagineni V, Ravi A, Datar IJ, Mino-Kenudson M, Corredor G, Barrera C, Behlman L, Rimm DL, Herbst RS, Madabhushi A, Riess JW, Velcheti V, Hellmann MD, Gainor J, Schalper KA. Role of tumor infiltrating lymphocytes and spatial immune heterogeneity in sensitivity to PD-1 axis blockers in non-small cell lung cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e004440. PMID: 35649657, PMCID: PMC9161072, DOI: 10.1136/jitc-2021-004440.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerImmune checkpoint inhibitorsT-cell immunoglobulin mucin-3Cell lung cancerCytotoxic T cellsT cellsImmune heterogeneityLung cancerT cell exhaustion marker expressionPD-L1 positive patientsT cell exhaustion markersAdaptive antitumor immune responsesCell death protein 1Baseline tumor samplesExhaustion marker expressionIndependent NSCLC cohortsTumor immune heterogeneityT-cell densityAntitumor immune responseT cell infiltrationDeath protein 1Multi-institutional cohortActivation gene-3Helper T cellsRole of tumorFirst report of safety/tolerability and preliminary antitumor activity of CAN-2409 in inadequate responders to immune checkpoint inhibitors for stage III/IV NSCLC.
Aggarwal C, Haas A, Gordon S, Mehra R, Lee P, Bestvina C, Maldonado F, Velcheti V, Herbst R, Bell S, Gillmor R, Manzanera A, Matheny C, Aguilar-Cordova E, Aguilar L, Barone F, Tak P, Sterman D. First report of safety/tolerability and preliminary antitumor activity of CAN-2409 in inadequate responders to immune checkpoint inhibitors for stage III/IV NSCLC. Journal Of Clinical Oncology 2022, 40: 9037-9037. DOI: 10.1200/jco.2022.40.16_suppl.9037.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsStage III/IV NSCLCProgressive diseaseClinical responseAdvanced NSCLCEvaluable patientsCheckpoint inhibitorsInjected tumorsDisease-positive lymph nodesNon-injected lesionsSafety/tolerabilitySubset of patientsT cell infiltrationPreliminary antitumor activityPreliminary clinical dataTumor cell lysisMedicine clinical trialsRational combination approachesIntra-tumoral deliveryStable diseaseData cutoffDisease stabilizationImmunologic biomarkersOral valacyclovirMedian duration
2019
Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer
Zugazagoitia J, Liu Y, Toki M, McGuire J, Ahmed FS, Henick BS, Gupta R, Gettinger S, Herbst R, Schalper KA, Rimm DL. Quantitative Assessment of CMTM6 in the Tumor Microenvironment and Association with Response to PD-1 Pathway Blockade in Advanced-Stage Non–Small Cell Lung Cancer. Journal Of Thoracic Oncology 2019, 14: 2084-2096. PMID: 31605795, PMCID: PMC6951804, DOI: 10.1016/j.jtho.2019.09.014.Peer-Reviewed Original ResearchConceptsPD-L1CMTM6 expressionPathway blockadeAdvanced stage non-small cell lung cancerNon-small cell lung cancerPD-1 pathway blockadeTumor cellsAbsence of immunotherapyMultiplexed quantitative immunofluorescencePD-L1 coexpressionStromal immune cellsPD-L1 expressionT cell infiltrationLonger overall survivalCell lung cancerIndependent retrospective cohortsKRAS mutational statusExpression of CMTM6MARVEL transmembrane domainNSCLC cohortOverall survivalRetrospective cohortAxis blockadeClinical featuresImmunotherapy outcomes