2021
A reservoir of stem-like CD8+ T cells in the tumor-draining lymph node preserves the ongoing anti-tumor immune response
Connolly KA, Kuchroo M, Venkat A, Khatun A, Wang J, William I, Hornick NI, Fitzgerald BL, Damo M, Kasmani MY, Cui C, Fagerberg E, Monroy I, Hutchins A, Cheung JF, Foster GG, Mariuzza DL, Nader M, Zhao H, Cui W, Krishnaswamy S, Joshi NS. A reservoir of stem-like CD8+ T cells in the tumor-draining lymph node preserves the ongoing anti-tumor immune response. Science Immunology 2021, 6: eabg7836. PMID: 34597124, PMCID: PMC8593910, DOI: 10.1126/sciimmunol.abg7836.Peer-Reviewed Original ResearchConceptsTumor-specific CD8T cellsTumor microenvironmentOngoing anti-tumor immune responseChronic lymphocytic choriomeningitis virus (LCMV) infectionTumor-draining lymph nodesAnti-tumor immune responseLymphocytic choriomeningitis virus infectionIntratumoral T cellsEfficacy of immunotherapyT cell responsesTumor-draining lymphAntitumor T cellsT cell terminal differentiationStem-like CD8Immunologic shiftGene expression signaturesLymph nodesTerminal differentiationLung tumorsVirus infectionLung adenocarcinomaImmune responseCD8Cell responsesBone marrow NG2+/Nestin+ mesenchymal stem cells drive DTC dormancy via TGF-β2
Nobre A, Risson E, Singh D, Di Martino J, Cheung J, Wang J, Johnson J, Russnes H, Bravo-Cordero J, Birbrair A, Naume B, Azhar M, Frenette P, Aguirre-Ghiso J. Bone marrow NG2+/Nestin+ mesenchymal stem cells drive DTC dormancy via TGF-β2. Nature Cancer 2021, 2: 327-339. PMID: 34993493, PMCID: PMC8730384, DOI: 10.1038/s43018-021-00179-8.Peer-Reviewed Original ResearchConceptsMesenchymal stem cellsDTC dormancyHematopoietic stem cell quiescenceStem cellsStem cell quiescenceBone morphogenetic proteinTGF-β2Niche homeostasisMorphogenetic proteinsCell quiescenceBone marrow microenvironmentGenetic depletionP27 inductionDormancyConditional knockoutMarrow microenvironmentMetastatic outgrowthEstrogen receptor-positive BCExtrinsic factorsGrowth factorCellsTumor cellsBone relapseSystemic recurrenceBreast cancer
2020
Inducible de novo expression of neoantigens in tumor cells and mice
Damo M, Fitzgerald B, Lu Y, Nader M, William I, Cheung JF, Connolly KA, Foster GG, Akama-Garren E, Lee DY, Chang GP, Gocheva V, Schmidt LM, Boileve A, Wilson JH, Cui C, Monroy I, Gokare P, Cabeceiras P, Jacks T, Joshi NS. Inducible de novo expression of neoantigens in tumor cells and mice. Nature Biotechnology 2020, 39: 64-73. PMID: 32719479, PMCID: PMC7854852, DOI: 10.1038/s41587-020-0613-1.Peer-Reviewed Original ResearchConceptsT cell responsesLevel of regulationRNA splicingDNA recombinationGenetic regulationTolerance mechanismsInducible expressionNeoantigen expressionCell responsesNaïve T-cell responsesCD4 T cell responsesTumor cell linesPeripheral tolerance mechanismsT cell toleranceCentral T cell toleranceCell linesExpressionNovo expressionTight controlEndogenous CD8Antitumor immunityPeripheral toleranceAutoimmune diseasesT cellsThymus results