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Role of Dendritic Cells in a Mouse Model of Lung Carcinoma Rosalinda Sorrentino and Aldo Pinto

Role of Dendritic Cells in a Mouse Model of Lung Carcinoma Rosalinda Sorrentino and Aldo Pinto Department of Pharmacy (DIFARMA), University of Salerno, Fisciano , 84084, Italy. Carcinogen , Genetic alterations , etc. Lung cancer is one of the leading causes of death worldwide. . T cell.

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Role of Dendritic Cells in a Mouse Model of Lung Carcinoma Rosalinda Sorrentino and Aldo Pinto

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  1. RoleofDendriticCells in a MouseModelofLung Carcinoma • RosalindaSorrentinoand Aldo Pinto • Department of Pharmacy (DIFARMA), University of Salerno, Fisciano, 84084, Italy

  2. Carcinogen, Geneticalterations, etc. Lung cancer is one of the leading causes of death worldwide. T cell EpithelialCells Macrophage Dendritic Cell LungInjury/ChronicInflammation Chemotherapy: • Doxorubicin , Oxaliplatinum, Cisplatinum, Paclitaxel, Mitomycin C, etc. • Gefitinib, Crizotinib • …..however, low survivalpercentageisstillcounted…..

  3. Aim: Can wepharmacologicallymanipulateDCs to counterTumor Cell Growth??? • Melief CJ. Nature2005; 437, 41-42

  4. ImmunoeditingStudies: To evaluate the role of DCs on TumorOutgrowth 1. Tumor Cell Implantation LLC1 (2x105 cells) B16-F10 (1x105 cells) Day13 6-8 weeks old Day17 10 Dayslater Sacrifice i.p. Treatment with TLR ligands i.v. Injection • H&E and immunohistochemicalAnalyses • ELISAs on BAL and LungHomogenates • Flow CytometryAnalyses • SortingCells 2. Adoptive Transfer of BoneMarrow/Spleen/Lung-DerivedCells 7-Day Cell Culture Naive Mice i.v. A) Tumor-implanted Mice TLR ligand Treatment O/N Day13 BMDCs or Spleen-derivedcells Sacrifice Day17 Day10 Tumor-implanted Mice B) Naive Mice Lung-derivedDCs Sacrifice 24-72hours later Day10 i.v.

  5. ImmunoeditingStudies: To evaluate the role of DCs on Tumor Establishment/Progression Sacrifice at: 3-7-30 days Week 1 i.t. NMU 50µg/mouse Week 2 i.t. NMU 10µg/mouse Week 3 i.t. NMU 10µg/mouse 6-12 weeks old LungCancerProgression ChronicInflammation/LungCancer establishment Healthy LK B220-PE CD123-APC

  6. Grazie per l’Attenzione!!!

  7. Th1 polarization A. IFN I IFNAR mDCs pDCs NK cells IL-12p70 CTL response Stimulus IFN I PLASMACELL B. IFNAR B cell pDCs IL-6R IL-6 Y Y Y Y Stimulus Y Y CD27 IMMUNOCOMPLEXES CD70 CD80 or CD86 or PDL1 C. Immune-suppression pDCs CTLA-4 or PD-1 IDO Stimulus T cell Death KYNURENINES T Reg-cell

  8. pDCs Th2 response Th1 response Tcresponse Immunity Tolerance Tumor Progression Tumor Regression

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