Development of tumor immunoactivation therapy targeting soluble CD155

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02708
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: University of Tsukuba
• Principal Investigator: Shibuya Kazuko 筑波大学, 医学医療系, 教授 (00302406)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 腫瘍免疫 / 免疫逃避 / 免疫受容体 / 分子標的療法

Outline of Final Research Achievements

Tumor immune responses are regulated by the balance between activating and inhibitory signals to immune cells. In recent years, immune checkpoint inhibitors (ICIs), drugs that block inhibitory signals, have attracted attention as a new cancer therapy. However, their efficacy has been limited as the number of cases has accumulated. This suggests that blocking inhibitory signals by ICI alone is not sufficient to enhance tumor immune responses and that enhancing activation signals to immune cells is important.
The interaction of the activating receptor DNAM-1 expressed on immune cells with CD155 on tumors activates the tumor immune response. Human CD155 has a splicing variant, soluble CD155 (sCD155). We found that tumor-produced sCD155 suppresses tumor immune responses and promotes tumor growth and metastasis by inhibiting DNAM-1-mediated activation signals. This suggested that targeting sCD155 could enhance the activation signal of tumor immune response.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

腫瘍免疫応答は、免疫細胞への活性化シグナルと抑制性シグナルのバランスで制御されている。抑制性シグナルを阻止する薬剤である免疫チェックポイント阻害剤は、新しいがんの治療法として注目された。しかし、症例を積み重ねるに従って効果が限定的であることが示され、新たな腫瘍免疫活性化剤の開発が待たれている。私たちは腫瘍から産生される可溶型CD155 (sCD155)が活性化受容体DNAM-1のシグナルを阻害することで、腫瘍免疫応答を抑制し、腫瘍の増殖や転移を促進していることを明らかにした。このことより、sCD155標的療法は、腫瘍免疫応答の活性化シグナルを増強する新しいがん治療法となることが期待される。