2022 Fiscal Year Final Research Report
Microenviroment in classical Hodgkin lymphoma and Hodgkin-like ATLL
| Project/Area Number |
20K07381
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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 49020:Human pathology-related
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| Research Institution | Kurume University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 成人ヒトT細胞白血病・リンパ腫 / ホジキン様リンパ腫 / ホジキンリンパ腫 / 空間プロファイリング / 遺伝子発現解析 |
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| Outline of Final Research Achievements |
Hodgkin-like adult T-cell leukemia/lymphoma (ATLL) is a special subtype of ATLL harboring Hodgkin and Reed-Sternberg (HRS)-like cells and small to medium CD4+ T cells infected with human T-cell lymphotropic virus type I. We performed digital spatial profiling (DSP) and immunohistochemistry (IHC) to analyze the interaction between HRS-like cells and CD4+ T cells in Hodgkin-like ATLLs. DSP revealed significantly higher expression of co-stimulatory molecules, CD28 and inducible T-cell co-stimulator (ICOS), in CD4+ T cells surrounding HRS-like cells than in those away from HRS-like cells. IHC identified distinct CD4+ T cells expressing CD28, ICOS, and various inhibitory immune checkpoint molecules in a rosette-like manner around HRS-like cells. HRS-like cells expressed CD80 and CD86, the ligands of CD28. Our findings indicate the interaction between HRS-like cells and CD4+ T cells via co-stimulatory and immune checkpoint molecules in Hodgkin-like ATLL.
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| Free Research Field |
病理学
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| Academic Significance and Societal Importance of the Research Achievements |
ホジキン様成人ヒトT細胞白血病・リンパ腫（ホジキン様ATLL）はホジキンリンパ腫に類似した病理組織像を示すが、ホジキンリンパ腫の患者と比較して化学療法に不応なことが多く、予後は不良である。我々の研究成果でこれまで不明であったホジキン様リンパ腫の免疫微小環境が明らかになり、ホジキンリンパ腫と類似した共刺激分子ならび免疫チェックポイント分子によるHRS様細胞とCD4陽性細胞の相互作用が重要であることが示唆された。これらの分子に対する分子標的治療がホジキン様リンパ腫に有用である可能性を提示した。
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