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Role of Dendritic Cells in a Mouse Model of Lung Carcinoma Rosalinda Sorrentino and Aldo Pinto PowerPoint Presentation
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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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slide1

RoleofDendriticCells in a MouseModelofLung Carcinoma

  • RosalindaSorrentinoand Aldo Pinto
  • Department of Pharmacy (DIFARMA), University of Salerno, Fisciano, 84084, Italy
slide2

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…..
slide3

Aim: Can wepharmacologicallymanipulateDCs to counterTumor Cell Growth???

  • Melief CJ. Nature2005; 437, 41-42
slide4

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.

slide5

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

slide7

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

slide8

pDCs

Th2 response

Th1 response

Tcresponse

Immunity

Tolerance

Tumor

Progression

Tumor

Regression