2020 Fiscal Year Research-status Report
SMAD-STAT immune signaling network in lung cancer microenvironment
| Project/Area Number |
19K16699
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
尹 晶煥 東京医科大学, 医学部, 兼任助教 (30748885)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | Lung cancer / Anti-tumor immunity / Dendritic cell / T cell / TGF-beta / SMADs / STATs |
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| Outline of Annual Research Achievements |
<Plan 1: Roles of SMADs in DCs and T cells in immune homeostasis> I found that T cell and DC-specific Smad2 and Smad4 deficient mice showed normal immune phenotypes, whereas Smad3 KO mice showed deficiency in a certain DC subset in the steady-state condition.
<Plan 2: Roles of SMADs in DCs and T cells in lung cancer> I have applied the mouse Lewis lung carcinoma metastasis model: Ex3LL-luc to T cell and DC-specific Smad2 and Smad4 deficient mice. Clinical courses have been evaluated by IVIS imaging system.
<Plan 3: Effects of SMAD deficiency on STAT signaling in DCs and T cells in lung cancer> I have found that SMAD2 deficient conventional DCs upregulated the differentiation and anti-lung cancer functions of cytotoxic T cells in Ex3LL-luc-bearing mice.
<Plan 4: Mechanisms how SMAD-STAT signaling networks regulate DCs and T cells in anti-lung cancer immunity> I have discovered the novel regulatory interaction between STAT and SMADs in T cell and DC differentiation in lung cancer microenvironment. I have generated the adeno-associated virus vectors expressing the various constitutively active or inactive mutants of SMADs and STAT3 to elucidate the molecular mechanisms of SMAD-STAT signaling networks.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
As stated in the summary, I have made progress in accordance with the proposed plans.
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| Strategy for Future Research Activity |
I will finish revising the submitted manuscript on the role of SMAD3 in DC development <Plan 1>. I will finish <Plan 2> and <Plan 3> to submit the second manuscript of this project. To complete <Plan 4>, I will perform ChIP sequencing and RNA-sequencing of effector T cells and DCs from Ex3LL-luc-bearing mice (Macrogen, Korea).
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| Causes of Carryover |
Due to the pandemic, I could not spend all the FY2020 budget. I will make a payment with the balance mainly for sequencing.
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