The role of humoral immunity in tumor microenvironment
| Project/Area Number |
19K07657
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 腫瘍 / 免疫 / T細胞 / Fcレセプター / 抗体 |
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| Outline of Research at the Start |
これまで申請者は腫瘍と炎症にフォーカスを当て研究し腫瘍微小環境における様々な抑制性細胞、分子を報告してきた。特に近年、腫瘍周辺の免疫細胞の抗体産生系も活性化していることを発見し報告している。この腫瘍特異的抗体が腫瘍免疫においてどのような役割を果たしているか明らかになっていないが我々はFcレセプターを介し抑制性の免疫環境を誘導していること見いだしている。抗体を介した抑制性免疫の誘導は明らかになっておらず、このメカニズムを解明することが新しい創薬のターゲットとなることが期待されマウスを使用したトランスレーショナルな研究を経て、新たな癌免疫療法の開発につながるものと考えている。
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| 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.
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| 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。
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] Antibiotic Treatment Improves the Efficacy of Oxaliplatin-Based Therapy as First-Line Chemotherapy for Patients with Advanced Gastric Cancer: A Retrospective Study2022
Author(s)
Imai H, Saijo K, Komine K, Ueta R, Numakura R, Wakayama S, Umegaki S, Hiraide S, Kawamura Y, Kasahara Y, Ohuchi K, Takahashi M, Takahashi S, Shirota H, Takahashi M, Ishioka C.
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Journal Title
Cancer Manag Res
Volume: 14
Pages: 1259-1266
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Cisplatin Plus Capecitabine After Adjuvant S-1 in Metastatic Gastric Cancer: A Phase II T-CORE1102 Trial2022
Author(s)
Yoshioka T, Takahashi M, Sakamoto Y, Okita A, Fukui T, Murakawa Y, Shindo Y, Imai H, Ohori H, Shirota H, Chiba N, Sasahara YI, Nomura T, Fukushima N, Yamaguchi T, Shimodaira H, Ishioka C.
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Journal Title
Anticancer Res.
Volume: 126
Issue: 4
Pages: 2009-20015
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Wide-Targeted Metabolome Analysis Identifies Potential Biomarkers for Prognosis Prediction of Epithelial Ovarian Cancer2021
Author(s)
Hishinuma E, Shimada M, Matsukawa N, Saigusa D, Li B, Kudo K, Tsuji K, Shigeta S, Tokunaga H, Kumada K, Komine K, Shirota H, Aoki Y, Motoike IN, Yasuda J, Kinoshita K, Yamamoto M, Koshiba S, Yaegashi N.
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Journal Title
Toxins (Basel).
Volume: 13
Issue: 7
Pages: 461-461
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A phase 2 basket trial of combination therapy with trastuzumab and pertuzumab in patients with solid cancers harboring human epidermal growth factor receptor 2 amplification (JUPITER trial)2020
Author(s)
K. Takahashi, E. Ishibashi, T. Kubo, Y. Harada, H. Hayashi, M. Kano, Y. Shimizu, H. Shirota, Y. Mori, M. Muto, C. Ishioka, H. Dosaka-Akita, H. Matsubara, H. Nishihara, N. Sueoka-Aragane, S. Toyooka, A. Hirakawa, U. Tateishi, S. Miyake, S. Ikeda
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Journal Title
Medicine (Baltimore)
Volume: 99
Issue: 32
Pages: e21457-e21457
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Antibiotic therapy augments the efficacy of gemcitabine-containing regimens for advanced cancer: a retrospective study.2019
Author(s)
Imai H, Saijo K, Komine K, Otsuki Y, Ohuchi K, Sato Y, Okita A, Takahashi M, Takahashi S, Shirota H, Takahashi M, Ishioka C.
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Journal Title
Cancer Manag Res.
Volume: 11
Pages: 7953-7965
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Therapeutic Benefits of Ipilimumab among Japanese Patients with Nivolumab-Refractory Mucosal Melanoma: A Case Series Study.2019
Author(s)
Saijo K, Imai H, Ouchi K, Okada Y, Sato Y, Komine K, Takahashi M, Takahashi S, Shirota H, Takahashi M, Ishioka C.
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Journal Title
Tohoku J Exp Med.
Volume: 248
Issue: 1
Pages: 37-43
DOI
NAID
Related Report
Peer Reviewed / Open Access
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