2022
Resistance Mechanisms to Anti-PD Cancer Immunotherapy
Vesely MD, Zhang T, Chen L. Resistance Mechanisms to Anti-PD Cancer Immunotherapy. Annual Review Of Immunology 2022, 40: 45-74. PMID: 35471840, DOI: 10.1146/annurev-immunol-070621-030155.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAnti-PD therapyCancer immunotherapyMechanisms of resistanceImmune inhibitory moleculesFraction of patientsResistance mechanismsNormalization cancer immunotherapyAdditional immunotherapyPD-1Clinical evidenceAntigen presentationT cellsSolid tumorsTherapy resistanceH1 pathwayTumor microenvironmentImmunotherapyInhibitory moleculesHematopoietic malignanciesCancer treatmentTherapyPatientsCurrent studyCancer dataMalignancy
2021
Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy
Sun Y, Chen W, Torphy RJ, Yao S, Zhu G, Lin R, Lugano R, Miller EN, Fujiwara Y, Bian L, Zheng L, Anand S, Gao F, Zhang W, Ferrara SE, Goodspeed AE, Dimberg A, Wang XJ, Edil BH, Barnett CC, Schulick RD, Chen L, Zhu Y. Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy. Science Translational Medicine 2021, 13 PMID: 34321321, PMCID: PMC8749958, DOI: 10.1126/scitranslmed.abc8922.Peer-Reviewed Original ResearchConceptsInsulin-like growth factor binding protein 7Vascular dysfunctionAnti-programmed death-1/Intratumoral effector T cellsTumor vasculatureTumor microenvironmentGrowth factor binding protein 7Tumor-associated endothelial cellsImproved antitumor responsesEffector T cellsDeath-1/Immune checkpoint therapyImmune cell infiltrationFavorable tumor microenvironmentMouse tumor modelsBinding protein 7Checkpoint therapyAntitumor responseCell infiltrationPoor responseT cellsHypoxic tumor microenvironmentTumor perfusionSolid tumorsTherapeutic interventionsA Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy
Sanmamed MF, Nie X, Desai SS, Villaroel-Espindola F, Badri T, Zhao D, Kim AW, Ji L, Zhang T, Quinlan E, Cheng X, Han X, Vesely MD, Nassar AF, Sun J, Zhang Y, Kim TK, Wang J, Melero I, Herbst RS, Schalper KA, Chen L. A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy. Cancer Discovery 2021, 11: 1700-1715. PMID: 33658301, PMCID: PMC9421941, DOI: 10.1158/2159-8290.cd-20-0962.Peer-Reviewed Original ResearchConceptsNon-small cell lung cancerTumor-infiltrating lymphocytesExhausted T cellsTIL subsetsTumor microenvironmentCancer immunotherapyT cellsAdvanced non-small cell lung cancerPatient-derived tumor xenograft modelAnti-PD therapyT cell subsetsCell lung cancerPotential tissue biomarkersBaseline tumor tissueLung cancer tissuesSingle-cell mass cytometryTumor xenograft modelApoptotic CD8Dysfunctional CD8Immunotherapy resistancePD-1Activation markersAdjacent nontumoral tissuesPathway-dependent mannerLung cancer
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 ablation
2018
A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization
Sanmamed MF, Chen L. A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization. Cell 2018, 175: 313-326. PMID: 30290139, PMCID: PMC6538253, DOI: 10.1016/j.cell.2018.09.035.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsCancer immunotherapyImmune normalizationFrequent immune-related adverse eventsB7-H1/PDHigher objective response rateFuture cancer immunotherapyObjective response rateRare objective responsesAntitumor immune responseImmune activation mechanismsObjective responseAdverse eventsImmune enhancementTumor responseImmune deficiencyCancer indicationsDifferent therapiesImmune responseToxicity profileImmunotherapyResponse rateFDA approvalTumor microenvironmentDistinct mechanisms