The role of humoral immunity in tumor microenvironment

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07657
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Tohoku University
• Principal Investigator: Shirota Hidekazu 東北大学, 医学系研究科, 准教授 (50451555)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 腫瘍 / 免疫 / T細胞 / Fcレセプター / 抗体

Outline of Final Research Achievements

Various immune cells are recruited in the tumor microenvironment. It is well established that cellular immune responses, such as cytotoxic or suppressive activities, play an important role in regulating tumor growth and metastasis. However, the contribution of humoral immune responses against tumors is poorly understood. Fc receptors constitute critical elements for the up- or downregulation of immune responses through immune complexes. Here, we examined the potential role of the inhibitory Fc receptor, FcγRIIB, in tumor immunity using a mouse model. Our findings indicated that tumor-specific antibodies are induced in tumor-bearing mice and control tumor immunity. FcγRIIB deletion improved both cellular and humoral immunity against tumors and delayed tumor growth. These findings indicated that spontaneous antibodies against tumors create a suppressive tumor microenvironment through FcγRIIB signaling, thus suggesting an attractive therapeutic target for cancer immunotherapy.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

腫瘍微小環境において様々な免疫細胞、免疫活性化・抑制分子が関わっていることが明らかになりそれらをターゲットにした新規分子標的治療薬開発が進められている。腫瘍細胞に対して内因性に産生される腫瘍特異的抗体が、腫瘍微小環境に与える影響を FcγRIIB欠損マウスで検討した。本研究により内因性の腫瘍特異的抗体は FcγRIIB を介して抑制性の腫瘍微小環境形成に関与していることが示唆された。この経路は新たな治療標的となる可能性があり今後の創薬において免疫療法の優れたターゲットになることが示唆された。今後、ヒトへの検証が必要と考える。