Development of Innovative Therapy for Canine Cutaneous T-Cell Lymphoma by Targeting Chemokine Receptors

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03147
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Gifu University
• Principal Investigator: Maeda Sadatoshi 岐阜大学, 応用生物科学部, 教授 (50377694)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 皮膚リンパ腫 / ケモカイン

Outline of Final Research Achievements

Clonality analysis of canine cutaneous T-cell lymphoma (CTCL) lesions showed that heterogeneous clonality occurred outside the skin, indicating that tumor cells may be migrating systemically. Transplantation of EO-1 with knockout of the CCR4 or CCR7 genes into mice resulted in suppression of skin nodules and systemic metastasis . Furthermore, CCL17, CCL19, CCL21 or CCL22 promoted EO-1 proliferation, and knockout of CCR4 or CCR7 abolished these promoting effects. These results indicate that CCR4 and CCR7 promote not only tumor cell migration but also proliferation and are useful as therapeutic target molecules for canine CTCL.

Free Research Field

皮膚免疫

Academic Significance and Societal Importance of the Research Achievements

ケモカインはヒトと同様に犬CTCLにおいても重要であることが明らかとなり、ケモカインに着目したヒトCTCLの新規診断または治療法開発において犬が有用な動物モデルであることが示された。また、CCR4のみならずCCR7も病態に関与していること、腫瘍細胞の遊走のみならず増殖にも関与していることなどが明らかとなり、治療標的分子として重要であることが示された。