2021
Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses
Cui C, Wang J, Fagerberg E, Chen PM, Connolly KA, Damo M, Cheung JF, Mao T, Askari AS, Chen S, Fitzgerald B, Foster GG, Eisenbarth SC, Zhao H, Craft J, Joshi NS. Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses. Cell 2021, 184: 6101-6118.e13. PMID: 34852236, PMCID: PMC8671355, DOI: 10.1016/j.cell.2021.11.007.Peer-Reviewed Original ResearchConceptsCD8 TB cellsTfh cellsLung adenocarcinomaTfh-B cell interactionsTumor-specific B cellsFollicular helper cellsAnti-tumor immunityB cell signaturesCell effector functionsGerminal center formationGC B cellsCD4 THelper cellsTumor controlTumor neoantigensEffector functionsCell collaborationCell responsesCell signatureTumor cellsSignature correlatesNeoantigensCell functionCD4A 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 responses
2019
Stereotactic Body Radiation and Interleukin-12 Combination Therapy Eradicates Pancreatic Tumors by Repolarizing the Immune Microenvironment
Mills B, Connolly K, Ye J, Murphy J, Uccello T, Han B, Zhao T, Drage M, Murthy A, Qiu H, Patel A, Figueroa N, Johnston C, Prieto P, Egilmez N, Belt B, Lord E, Linehan D, Gerber S. Stereotactic Body Radiation and Interleukin-12 Combination Therapy Eradicates Pancreatic Tumors by Repolarizing the Immune Microenvironment. Cell Reports 2019, 29: 406-421.e5. PMID: 31597100, PMCID: PMC6919969, DOI: 10.1016/j.celrep.2019.08.095.Peer-Reviewed Original ResearchConceptsStereotactic body radiation therapyMultiple preclinical mouse modelsPancreatic ductal adenocarcinoma patientsEffective neoadjuvant therapyAdvanced metastatic diseaseStereotactic body radiationDuctal adenocarcinoma patientsLate-stage diseaseInterferon-gamma productionBody radiation therapySystemic tumor immunityPreclinical mouse modelsNeoadjuvant approachNeoadjuvant therapyLiver metastasesMetastatic diseaseCD8 TTumor immunityAdenocarcinoma patientsImmune microenvironmentTumor reductionMS administrationTherapy resultsPancreatic tumorsGamma production
2016
Increasing the efficacy of radiotherapy by modulating the CCR2/CCR5 chemokine axes
Connolly K, Belt B, Figueroa N, Murthy A, Patel A, Kim M, Lord E, Linehan D, Gerber S. Increasing the efficacy of radiotherapy by modulating the CCR2/CCR5 chemokine axes. Oncotarget 2016, 5: 86522-86535. PMID: 27852031, PMCID: PMC5349932, DOI: 10.18632/oncotarget.13287.Peer-Reviewed Original ResearchConceptsEfficacy of radiotherapyImmune responseSyngeneic tumor cell linesCancer typesIntratumoral immune infiltrateAnti-tumor immunityIntratumoral immune responseEffect of radiotherapyMechanism of radiotherapyEffectiveness of radiotherapyChemokine axesRadioresponsive tumorsLocal radiotherapyImmunosuppressive cellsImmune infiltratesRT failureTumor recurrenceImmune cellsCCR5 antagonistsMurine modelHigh incidenceRadiotherapyTumor growthRT efficacyTumor site