2022
S220 High Intratumoral Hepatovirus Abundance in Colon Adenocarcinoma Is Associated With Worse Overall Survival and Increased Intratumoral CD8+ T-Cell Infiltration
Chen G, Zaman S, Segarra D, Patel A, Protiva P. S220 High Intratumoral Hepatovirus Abundance in Colon Adenocarcinoma Is Associated With Worse Overall Survival and Increased Intratumoral CD8+ T-Cell Infiltration. The American Journal Of Gastroenterology 2022, 117: e158-e158. DOI: 10.14309/01.ajg.0000857520.28843.4b.Peer-Reviewed Original ResearchInduction of the activating transcription factor-4 in the intratumoral CD8+ T cells sustains their viability and anti-tumor activities
Lu Z, Bae E, Verginadis I, Zhang H, Cho C, McBrearty N, George S, Diehl J, Koumenis C, Bradley L, Fuchs S. Induction of the activating transcription factor-4 in the intratumoral CD8+ T cells sustains their viability and anti-tumor activities. Cancer Immunology, Immunotherapy 2022, 72: 815-826. PMID: 36063172, PMCID: PMC10317204, DOI: 10.1007/s00262-022-03286-2.Peer-Reviewed Original ResearchConceptsActivity of CD8Tumor-derived factorsT cellsTumor microenvironmentTranscription factor 4Anti-tumor immunityImmune suppressive factorsFactor 4Anti-tumor activityFunction of ATF4Anti-cancer therapyIntratumoral CD8Cytotoxic CD8Immune therapyTherapeutic regimensAntigenic stimulationCD8Suppressive factorsT lymphocytesMouse modelImpaired activationWild-type counterpartsSelective ablationTherapyInduction of ATF4
2021
Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8+ T cells in tumors
Xu S, Chaudhary O, Rodríguez-Morales P, Sun X, Chen D, Zappasodi R, Xu Z, Pinto AFM, Williams A, Schulze I, Farsakoglu Y, Varanasi SK, Low JS, Tang W, Wang H, McDonald B, Tripple V, Downes M, Evans RM, Abumrad NA, Merghoub T, Wolchok JD, Shokhirev MN, Ho PC, Witztum JL, Emu B, Cui G, Kaech SM. Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8+ T cells in tumors. Immunity 2021, 54: 1561-1577.e7. PMID: 34102100, PMCID: PMC9273026, DOI: 10.1016/j.immuni.2021.05.003.Peer-Reviewed Original ResearchConceptsTumor microenvironmentCell dysfunctionLipid peroxidationLipid accumulationOxidized low-density lipoproteinExpression of CD36Low-density lipoproteinCommon metabolic alterationsScavenger receptor CD36Intratumoral CD8Immune dysfunctionEffector TGlutathione peroxidase 4CD8Effector functionsInhibition of p38Metabolic alterationsReceptor CD36Therapeutic avenuesScavenger receptorsDysfunctionWT counterpartsTILsCell functionCD36Atezolizumab and nab-Paclitaxel in Advanced Triple-Negative Breast Cancer: Biomarker Evaluation of the IMpassion130 Study
Emens LA, Molinero L, Loi S, Rugo HS, Schneeweiss A, Diéras V, Iwata H, Barrios CH, Nechaeva M, Nguyen-Duc A, Chui SY, Husain A, Winer EP, Adams S, Schmid P. Atezolizumab and nab-Paclitaxel in Advanced Triple-Negative Breast Cancer: Biomarker Evaluation of the IMpassion130 Study. Journal Of The National Cancer Institute 2021, 113: 1005-1016. PMID: 33523233, PMCID: PMC8328980, DOI: 10.1093/jnci/djab004.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerMetastatic triple-negative breast cancerProgression-free survivalPD-L1Tumor immune microenvironmentBreast cancerIntratumoral CD8Nab-paclitaxelClinical benefitImmune microenvironmentImmune cellsBRCA1/2 mutationsAdvanced triple-negative breast cancerStromal tumor-infiltrating lymphocytesNab-paclitaxel 100Immune checkpoint inhibitorsOverall survival benefitTumor-infiltrating lymphocytesMetastatic tumor tissueBRCA1/2 mutation statusCheckpoint inhibitorsOverall survivalSurvival benefitImmune biomarkersClinical activity
2018
KDM5 histone demethylases repress immune response via suppression of STING
Wu L, Cao J, Cai WL, Lang SM, Horton JR, Jansen DJ, Liu ZZ, Chen JF, Zhang M, Mott BT, Pohida K, Rai G, Kales SC, Henderson MJ, Hu X, Jadhav A, Maloney DJ, Simeonov A, Zhu S, Iwasaki A, Hall MD, Cheng X, Shadel GS, Yan Q. KDM5 histone demethylases repress immune response via suppression of STING. PLOS Biology 2018, 16: e2006134. PMID: 30080846, PMCID: PMC6095604, DOI: 10.1371/journal.pbio.2006134.Peer-Reviewed Original ResearchConceptsImmune responseSTING expressionCyclic GMP-AMP synthase stimulatorSuppression of STINGCancer cellsCancer immunotherapy agentsHuman papilloma virusAdaptive immune responsesMultiple clinical trialsExpression of STINGBreast cancer cellsInnate immune defenseRobust interferon responseMultiple cancer typesIntratumoral CD8Immunotherapy agentsAnticancer immunotherapyPatient survivalNeck cancerPapilloma virusClinical trialsT cellsSTING agonistsKDM5 histonePositive head
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