SMAD-STAT immune signaling network in lung cancer microenvironment

2019 Fiscal Year Research-status Report

• Project/Area Number: 19K16699
• Research Institution: Tokyo Medical University
• Principal Investigator: 尹 晶煥 東京医科大学, 医学部, 兼任助教 (30748885)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: Lung cancer / Anti-tumor immunity / Dendritic cell / T cell / TGF-beta / SMADs / STATs

Outline of Annual Research Achievements

<Plan 1: Roles of SMADs in DCs and T cells in lung mucosal immune homeostasis> T cell and DC-specific Smad2 and Smad4 deficient (KO) mice showed normal immune phenotypes. Smad3 KO mice showed deficiency in a DC subset at the steady-state condition.
<Plan 2: Roles of SMADs in DCs and T cells in lung cancer> I have established Lewis lung carcinoma cell line engineered to express GFP or the firefly luciferase gene (luc2) for orthotopic lung cancer model.
<Plan 3: Effects of SMAD deficiency on STAT signaling in DCs and T cells in lung cancer> I have found that increased conventional DCs (cDCs) by SMAD3 deficiency showed significantly enhanced phosphorylation of STAT3.
<Plan 4: Mechanisms how SMAD-STAT signaling networks regulate DCs and T cells in anti-lung cancer immunity> I have generated the various constitutively active or inactive mutants of SMADs or STAT3 using adeno-associated virus system.

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 a progress in accordance with the proposed plans.

Strategy for Future Research Activity

I will continue the research as proposed. I will finish revision of the submitted manuscript to publish the results on the role of SMAD3 on DC development (cf. Plan 1).

Causes of Carryover

Due to the pandemic, I could not spend all the fiscal budget. I will spend the balance for purchasing the antibodies and reagents required for the orthotopic Lewis lung carcinoma model and mechanistic studies this year.

Research Products

• [Presentation] SMAD3 Determines Conventional versus Plasmacytoid Dendritic Cell Fates (2019)
  • Author(s): Jeong-Hwan Yoon, Eunjin Bae, Jin Soo Han, Seok Hee Park, Susumu Nakae, InKyu Lee, Ji Hyeon Ju, Isao Matsumoto, Takayuki Sumida and Mizuko Mamura
  • Organizer: The 48th Annual Meeting of The Japanese Society for Immunology, Hamamatsu, Japan
  • Int'l Joint Research