Immunological approach to Th2-dominant tumor microenvironment in malignant lymphoma and new therapeutic strategies
Project/Area Number |
16K10146
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Dermatology
|
Research Institution | International University of Health and Welfare |
Principal Investigator |
SUGAYA MAKOTO 国際医療福祉大学, 医学部, 教授 (90334408)
|
Research Collaborator |
SHISHIDO NAOMI (TAKAHASHI NAOMI)
OKA TOMONORI
|
Project Period (FY) |
2016-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | 皮膚リンパ腫 / 腫瘍微小環境 / TSLP / ペリオスチン / CD137L / CD155 / CD226 / 制御性B細胞 / GATA6 / HMGB1 / プログラニュリン / IL-25 / IL-19 / IL-36 / 可溶性CD48 / VEGF / PlGF / 皮膚悪性リンパ腫 / ぺリオスチン / Th2サイトカイン / STAT5 / 腫瘍免疫 / リンパ腫 / Th2 / TARC |
Outline of Final Research Achievements |
Our research has revealed that TSLP, periostin, IL-36, IL-25, IL-19, and HMGB1 contribute to Th2-dominant tumor microenvironment in cutaneous T-cell lymphoma (CTCL). We have also found that CD137L, induced by overexpression of GATA6 on tumor cells, is important for survival, proliferation, and migration of CTCL tumor cells. Moreover, decrease in CD226 on the surface of immune cells contributes to progression of CTCL. VEGF-A and PlGF are associated with pruritus and angiogenesis in CTCL, respectively. These findings have deepened our understanding about tumor microenvironment and tumor immunity in CTCL, leading to new therapeutic strategies.
|
Academic Significance and Societal Importance of the Research Achievements |
悪性腫瘍において腫瘍細胞を取り巻く微小環境は、腫瘍の増殖にとって重要であり、ニボルマブに代表されるように治療ターゲットになる。我々は皮膚リンパ腫を研究材料としてTh2優位な腫瘍微小環境に関する研究を行い、多くのサイトカインが関与することを見出した。また腫瘍細胞の発現するCD137Lが腫瘍細胞の生存に寄与することが判明した。これらをターゲットにした治療が今後開発される可能性があり、また他の悪性腫瘍の治療やTh2優位な皮膚疾患の病態理解にも応用することが可能であり、大変有意義であったと考える。
|
Report
(4 results)
Research Products
(30 results)
-
[Journal Article] Increased expression of aquaporin-1 in dermal fibroblasts and dermal microvascular endothelial cells possibly contributes to skin fibrosis and edema in patients with systemic sclerosis.2019
Author(s)
Yamashita T, Asano Y, Saigusa R, Taniguchi T, Nakamura K, Miura S, Toyama T, Takahashi T, Ichimura Y, Hirabayashi M, Yoshizaki A, Miyagaki T, Sugaya M, Sato S.
-
Journal Title
J Dermatol Sci
Volume: 93
Issue: 1
Pages: 24-32
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
[Journal Article] Decreased IL-10-producing regulatory B cells in patients with advanced mycosis fungoides.2018
Author(s)
Akatsuka T, Miyagaki T, Nakajima R, Kamijo H, Oka T, Takahashi N, Suga H, Yoshizaki A, Asano Y, Sugaya M, Sato S.
-
Journal Title
Eur J Dermatol
Volume: 28
Issue: 3
Pages: 314-319
DOI
Related Report
Peer Reviewed
-
[Journal Article] The vitamin D3 analog, maxacalcitol, reduces psoriasiform skin inflammation by inducing regulatory T cells and downregulating IL-23 and IL-17 production.2018
Author(s)
Hau CS, Shimizu T, Tada Y, Kamata M, Takeoka S, Shibata S, Mitsui A, Asano Y, Sugaya M, Kadono T, Sato S, Watanabe S.
-
Journal Title
J Dermatol Sci.
Volume: 92
Issue: 2
Pages: 117-126
DOI
Related Report
Peer Reviewed
-
-
-
[Journal Article] Increased HMGB1 levels in lesional skin and sera in patients with cutaneous T-cell lymphoma.2018
Author(s)
Senda N, Miyagaki T, Kamijo H, Nakajima R, Oka T, Takahashi N, Suga H, Yoshizaki A, Asano Y, Sugaya M, Sato S.
-
Journal Title
Eur J Dermatol
Volume: 28
Pages: 621-627
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] ncreased endocan expression in lesional skin and decreased endocan expression in sera in atopic dermatitis.2017
Author(s)
Suzuki H, Miyagaki T, Otobe S, Nakajima R, Oka T, Takahashi N, Kabasawa M, Suga H, Yoshizaki A, Asano Y, Sato S, Sugaya M.
-
Journal Title
J Dermatol
Volume: 44
Issue: 12
Pages: 1392-1395
DOI
Related Report
Peer Reviewed
-
-
[Journal Article] Histone deacetylase inhibitors inhibit metastasis by restoring a tumor suppressive microRNA-150 in advanced cutaneous T-cell lymphoma.2017
Author(s)
Abe F, Kitadate A, Ikeda S, Yamashita J, Nakanishi H, Takahashi N, Asaka C, Teshima K, Miyagaki T, Sugaya M, Tagawa H.
-
Journal Title
Oncotarget
Volume: 8
Issue: 5
Pages: 7572-7585
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Hematopoietic stem cell transplantation for cutaneous T-cell lymphoma: Summary of 11 cases from two facilities in Japan and Brazil.2016
Author(s)
Oka T, Sugaya M, Cury-Martins J, Vasconcelos-Berg R, Suga H, Miyagaki T, Scheinberg P, Fujita H, Izutsu K, Sato S, Sanches JA.
-
Journal Title
Journal of Dermatology
Volume: 43(6)
Issue: 6
Pages: 638-642
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
[Journal Article] Decreased interleukin-21 expression in skin and blood in advanced mycosis fungoides.2016
Author(s)
Kabasawa M, Sugaya M, Oka T, Takahashi N, Kawaguchi M, Suga H, Miyagaki T, Takahashi T, Shibata S, Fujita H, Asano Y, Tada Y, Kadono T, Okochi H, Sato S.
-
Journal Title
Journal of Dermatology
Volume: 43(7)
Issue: 7
Pages: 819-822
DOI
Related Report
Peer Reviewed
-
-
[Journal Article] Increased syndecan-4 expression in sera and skin of patients with atopic dermatitis.2016
Author(s)
Nakao M, Sugaya M, Takahashi N, Otobe S, Nakajima R, Oka T, Kabasawa M, Suga H, Morimura S, Miyagaki T, Fujita H, Asano Y, Sato S.
-
Journal Title
Archives of Dermatological Research
Volume: 308(9)
Issue: 9
Pages: 655-660
DOI
Related Report
Peer Reviewed
-
-
-