大分大学医学部感染予防医学講座

　Astri Dewayani

	Astri Dewayani (M.D.) 大分大学医学部感染予防医学講座　大学院生	CD8+ cytotoxic T lymphocytes (CTLs) and CD4+ helper T (Th) cells play a critical role in protective immune responses to tumor cells. Particularly, Th9 cells exert anti-tumor activity by producing IL-9. TNF receptor (TNFR)-associated factor 6 (TRAF6) is an adaptor protein that mediates the signals from both the TNFR superfamily and Toll-like receptors (TLRs). It has been reported that T cell-specific TRAF6-deficent (TRAF6ΔT) mice spontaneously developed systemic inflammatory diseases. I have studied on the physiological role of TRAF6 in T cells in controlling anti-tumor immune responses and found that tumor formation of syngeneic colon cancer cells inoculated in TRAF6ΔT mice was accelerated compared to that in control mice. Although TRAF6-deficient naive T cells showed enhanced differentiation of Th9 cells in vitro, these T cells produced lower amounts of IL-9 in response to a specific antigen. Moreover, CD4+ tumor-infiltrating lymphocytes (TILs) in tumor-bearing TRAF6ΔT mice expressed lower levels of IL-9 than those in WT mice. Importantly, administration of recombinant IL-9 (rIL-9) strongly suppressed tumor progression in TRAF6ΔT mice. Furthermore, expression levels of the T-box transcription factor Eomesodermin (Eomes) and its target molecules IFN-gamma, granzyme B and perforin, as well as cytotoxic activity, were reduced in TRAF6-deficient CD8+ T cells in vitro. TRAF6-deficient T cells were found to express significantly increased levels of immune checkpoint molecules, CTLA-4 and PD-1 on the cell surface. These results demonstrate that the TRAF6 signaling pathway in T cells regulates anti-tumor immunity through the activation of tumor specific Th9 cells and CTLs in a tumor microenvironment.

Astri Dewayani (M.D.)

大分大学医学部感染予防医学講座　大学院生

CD8+ cytotoxic T lymphocytes (CTLs) and CD4+ helper T (Th) cells play a critical role in protective immune responses to tumor cells. Particularly, Th9 cells exert anti-tumor activity by producing IL-9. TNF receptor (TNFR)-associated factor 6 (TRAF6) is an adaptor protein that mediates the signals from both the TNFR superfamily and Toll-like receptors (TLRs). It has been reported that T cell-specific TRAF6-deficent (TRAF6ΔT) mice spontaneously developed systemic inflammatory diseases.
I have studied on the physiological role of TRAF6 in T cells in controlling anti-tumor immune responses and found that tumor formation of syngeneic colon cancer cells inoculated in TRAF6ΔT mice was accelerated compared to that in control mice. Although TRAF6-deficient naive T cells showed enhanced differentiation of Th9 cells in vitro, these T cells produced lower amounts of IL-9 in response to a specific antigen. Moreover, CD4+ tumor-infiltrating lymphocytes (TILs) in tumor-bearing TRAF6ΔT mice expressed lower levels of IL-9 than those in WT mice. Importantly, administration of recombinant IL-9 (rIL-9) strongly suppressed tumor progression in TRAF6ΔT mice. Furthermore, expression levels of the T-box transcription factor Eomesodermin (Eomes) and its target molecules IFN-gamma, granzyme B and perforin, as well as cytotoxic activity, were reduced in TRAF6-deficient CD8+ T cells in vitro. TRAF6-deficient T cells were found to express significantly increased levels of immune checkpoint molecules, CTLA-4 and PD-1 on the cell surface. These results demonstrate that the TRAF6 signaling pathway in T cells regulates anti-tumor immunity through the activation of tumor specific Th9 cells and CTLs in a tumor microenvironment.

Nationality: 　The Republic of Indonesia　

Research Project:
　Cancer Biology, Tumor Immunity

Supervisor: 　
　Dr. Kamiyama, Dr. Kobayashi

Education and Professional Experience:
　October 2018 - Present: Oita University Graduate School of Medicine (Ph.D. student)
　February 2021 - Present: DEPT. OF ANATOMY & HISTOLOGY, AIRLANGGA UNIVERSITY, SURABAYA (LECTURER)
　January 2018 - January 2021: DEPT. OF ANATOMY & HISTOLOGY, AIRLANGGA UNIVERSITY, SURABAYA (CONTRACT LECTURER)
　August 2010 - July 2016: MEDICAL FACULTY, AIRLANGGA UNIVERSITY

Scientific Society: 　　
　The Molecular Biology Society of Japan 日本分子生物学会

Publications: 　　
Dewayani A, Kamiyama N, Sachi N, Ozaka S, Saechue B, Arik S, Goto M, Chalalai T, Soga Y, Fukuda C, Kagoshima Y, Maekawa Y, Kobayashi T. TRAF6 signaling pathway in T cells regulates anti-tumor immunity through the activation of tumor specific Th9 cells and CTLs. Biochem Biophys Res Commun. (2022) in press.