2021 Fiscal Year Final Research Report
Effect of neutrophil extracellular traps on tumor infiltrating lymphocytes in gastrointestinal tumor
| Project/Area Number |
20K22960
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0905:Surgery of the organs maintaining homeostasis and related fields
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| Research Institution | Jichi Medical University |
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Principal Investigator |
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| Project Period (FY) |
2020-09-11 – 2022-03-31
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| Keywords | 好中球細胞外トラップ / 腫瘍浸潤リンパ球 / 消化器癌 / 免疫療法 / ケモカイン |
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| Outline of Final Research Achievements |
The phenomenon that PMA- or LPS-activated neutrophils involving NETs inhibited chemotaxis of T cells activated with anti-CD3 Ab and IL-2 to CXCL11 was confirmed. It is thought that some of the reasons were due to hydrogen peroxide inhibiting depolymerization of actin in PMA-activated neutrophils and degradation of chemokine via protease bound to NETs produce by LPS-activated. Moreover, Adding catalase to hydrolyze hydrogen peroxide restored reduced migration of T cells in PMA-activated neutrophils, while administrating DNase I for destruction of NETs or protease inhibitors such as NEI or PMSF inhibited degradation of CXCL11 by NETs and also restored migration.
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| Free Research Field |
消化器外科学、産科婦人科、腫瘍免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍浸潤リンパ球が多いと予後良好だが、 NETsを含めた腫瘍関連好中球が多いと予後不良であることが様々な癌腫において報告されている。近年NETsが癌の進展に関わっていることが解ってきたが、リンパ球浸潤に与える影響についてはほとんど解っていない。本研究ではNETsを含めた活性化好中球が活性化Tリンパ球のCXCL11に対する走化性を複数のメカニズムで抑制していることを示すことが出来た。好中球による過酸化水素とNETsの放出を抑制、分解することで腫瘍内へのリンパ球浸潤が期待でき、抗腫瘍効果を高め予後改善につながる可能性がある点で今後の癌免疫療の発展に繋がる重要な示唆が得られた。
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