Utility of tumor-draining lymph nodes as new source of cell therapy for colorectal cancer patients
| Project/Area Number |
20K16458
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
OKAMURA Kazumi 公益財団法人がん研究会, がんプレシジョン医療研究センター 免疫ゲノム医療開発プロジェクト, 研究員 (80768630)
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| Project Period (FY) |
2020-04-01 – 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: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
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| Keywords | 養子免疫療法 / 大腸癌 / T細胞受容体 / 所属リンパ節 / 腫瘍浸潤リンパ球 / リンパ節 / 養子細胞療法 |
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| Outline of Research at the Start |
大腸がん患者で手術時に同時に採取されるリンパ節中のリンパ球が、腫瘍浸潤リンパ球と同様腫瘍細胞を認識し抗腫瘍効果を発揮できるか、機能的な差、反応する抗原の多様性について検討を行う。これによりリンパ節中のリンパ球が新たな細胞療法における有効なソースとなりうるかを明らかにすることを目的とする。リンパ節内のリンパ球は腫瘍抗原への暴露状況の違いからより機能的細胞を得ることができることが期待される。
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| Outline of Final Research Achievements |
Tumor-draining lymph nodes are primary sites, where anti-tumor lymphocytes are primed to tumor-specific antigens and play pivotal roles in immune responses against tumors.
Lymphocytes from TDLNs resected during surgical operation were cultured with autologous-tumor cells for 2 weeks and evaluated tumor-reactivity by IFNγ ELISPOT assay. We investigated the commonality of T cell receptor (TCR) clonotypes expanded by the co-culture with tumor cells with those of tumor infiltrating lymphocytes (TILs). We found that that TCR clonotypes of PD-1-expressing CD8+ T cells in lymph nodes commonly shared with those of TILs in primary tumors and lymphocytes having tumor-reactivity and TCR clonotypes shared with TILs could be induced from non-metastatic lymph nodes when they were co-cultured with autologous tumor cells. Our results imply that tumor-reactive effector T cells were present and could be expanded in vitro in the presence of autologous tumor cells and possibly be applied for ACT.
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| Academic Significance and Societal Importance of the Research Achievements |
現在免疫療法、とりわけ細胞療法は効果が期待される治療法である反面、すべての患者に適応できる治療法とはなり得ていない。今回、手術時に同時に摘出したリンパ節を用いる事により多くの患者で抗腫瘍効果を持つリンパ球を体外で増幅でき、細胞療法が行える可能性が示された。自己の細胞を用いることによる、安全面、また経済的な面での優位性が高いだけでなく、リンパ節細胞の保存は簡便であり、再発時などの局面ですぐに適用できる治療法として期待される。
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Report
(3 results)
Research Products
(2 results)
