2022
Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer
Henick BS, Villarroel-Espindola F, Datar I, Sanmamed MF, Yu J, Desai S, Li A, Aguirre-Ducler A, Syrigos K, Rimm DL, Chen L, Herbst RS, Schalper KA. Quantitative tissue analysis and role of myeloid cells in non-small cell lung cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e005025. PMID: 35793873, PMCID: PMC9260844, DOI: 10.1136/jitc-2022-005025.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerSquamous cell carcinomaHuman non-small cell lung cancerMyeloid cell subsetsCell lung cancerHLA-DRLung adenocarcinomaMyeloid cellsCell subsetsLung cancerLung tissueQuantitative immunofluorescenceNon-tumor lung tissuesIndependent NSCLC cohortsLevels of CD68Multiplexed quantitative immunofluorescenceProinflammatory myeloid cellsHLA-DR expressionM1-like macrophagesImmature myeloid cell populationMyeloid cell populationsKRAS mutant tumorsNormal lung tissuesTumor epithelial cellsNon-tumor lungDevelopment of an immunohistochemical assay for Siglec-15
Shafi S, Aung TN, Robbins C, Zugazagoitia J, Vathiotis I, Gavrielatou N, Yaghoobi V, Fernandez A, Niu S, Liu LN, Cusumano ZT, Leelatian N, Cole K, Wang H, Homer R, Herbst RS, Langermann S, Rimm DL. Development of an immunohistochemical assay for Siglec-15. Laboratory Investigation 2022, 102: 771-778. PMID: 35459795, PMCID: PMC9253057, DOI: 10.1038/s41374-022-00785-9.Peer-Reviewed Original ResearchConceptsSiglec-15IHC assaysPD-L1PD-1/PD-L1 inhibitionPD-L1 blockadePD-L1 inhibitionHigh expressionFuture clinical trialsImmunoglobulin-type lectinsSiglec-15 expressionCompanion diagnostic assayPromising new targetTumor histologyImmunotherapeutic targetLung cancerImmune cellsClinical trialsNovel recombinant antibodiesCancer histologyImmunohistochemical assaysMyeloid cellsTumor typesScoring systemNew targetsHigh concordance
2019
Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy
Wang J, Sun J, Liu LN, Flies DB, Nie X, Toki M, Zhang J, Song C, Zarr M, Zhou X, Han X, Archer KA, O’Neill T, Herbst RS, Boto AN, Sanmamed MF, Langermann S, Rimm DL, Chen L. Siglec-15 as an immune suppressor and potential target for normalization cancer immunotherapy. Nature Medicine 2019, 25: 656-666. PMID: 30833750, PMCID: PMC7175920, DOI: 10.1038/s41591-019-0374-x.Peer-Reviewed Original ResearchConceptsNormalization cancer immunotherapyTumor microenvironmentSiglec-15Antibody blockadeCancer immunotherapyImmune suppressorMyeloid cellsAntigen-specific T cell responsesB7-H1/PDTumor-infiltrating myeloid cellsB7-H1 moleculesAnti-tumor immunityT cell responsesPotential targetImmune evasion mechanismsInhibits tumor growthMacrophage colony-stimulating factorColony-stimulating factorB7-H1Evasion mechanismsMouse modelHuman cancer cellsTumor growthCell responsesGenetic ablationConvergent Identification and Interrogation of Tumor-Intrinsic Factors that Modulate Cancer Immunity In Vivo
Codina A, Renauer PA, Wang G, Chow RD, Park JJ, Ye H, Zhang K, Dong MB, Gassaway B, Ye L, Errami Y, Shen L, Chang A, Jain D, Herbst RS, Bosenberg M, Rinehart J, Fan R, Chen S. Convergent Identification and Interrogation of Tumor-Intrinsic Factors that Modulate Cancer Immunity In Vivo. Cell Systems 2019, 8: 136-151.e7. PMID: 30797773, PMCID: PMC6592847, DOI: 10.1016/j.cels.2019.01.004.Peer-Reviewed Original ResearchConceptsSingle-cell transcriptomic profilingExtracellular protein productionCancer cellsMutant cellsFunctional interrogationGenetic programCRISPR screensTranscriptomic profilingTumor-intrinsic mutationsTranscriptomic alterationsTumor microenvironmentProtein productionPRKAR1A lossGenetic makeupHost myeloid cellsTumor-intrinsic factorsDrastic alterationsCytometry analysisConvergent identificationMyeloid cellsCellsImmunocompetent hostsCancer immunityMutant tumorsHost