Journal of hematology & oncology · 2022
Revealing the evolution of the tumor immune microenvironment in follicular lymphoma patients progressing within 24 months using single-cell imaging mass cytometry.
Письмо в редакциюПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Liu Long, Yu Xingxing, Li Zhifeng, He Xiaohua, Zha Jie, Lin Zhijuan, Hong Yan, Zheng Huijian, Lai Qian, Ding Kaiyang, Jia Xian, Fu Guo, Yu Haifeng, Yang Haiyan, Li Zhiming, Young Ken H, Xu Bing
Аннотация
BACKGROUND: Patients with follicular lymphoma (FL) who experience disease progression within 24 months (POD24) have inferior outcomes. The tumor immune microenvironment (TIME) plays a crucial role in pathogenesis and progression of follicular lymphoma (FL). However, TIME evolution during progression of disease within 24 months (POD24) is elusive.
METHODS: Spatially resolved and single-cell image mass cytometry with a panel of 36 metal-tagged antibodies was used to quantitatively analyze the TIME structure in 13 paired FLs at diagnosis and POD24.
RESULTS: Follicles and peri-follicular regions were well dissected in structure. Peri-follicular regions represented a barrier for immune infiltration into the follicles. More FL-cells in the peri-follicular regions suffered CD8+T cells attacks under simultaneous protection of regulatory T cells (Tregs) and/or macrophages compared with that in the follicles irrespective of POD24. During POD24, increased CD163- macrophages with PD-1 ligand upregulation and decreased CD8+T cells with upregulated LAG-3 expression around FL-cells were observed in the follicles. Spatial analyses demonstrated that FL-cells interacted more intimately with macrophages than with Tregs and less with cytotoxic T cells in both peri-follicular regions and follicles during POD24. In comparison, macrophages also cooperated more frequently with Tregs to simultaneously hijack FL-cells, creating an enhanced immunosuppressive environment in both peri-follicular and follicular regions during POD24.
CONCLUSIONS: Peri-follicular regions function as a barrier by recruiting both CD8+T cells and immunosuppressive cells, protecting follicular FL-cells from immune attack at diagnosis or POD24. FL-cells reside in a more immune-compromised microenvironment and evade immune cell attacks during POD24. Novel immunotherapeutic approaches harnessing LAG-3, macrophages, and Tregs will be empowered to overcome poor outcomes in patients with FL POD24.
METHODS: Spatially resolved and single-cell image mass cytometry with a panel of 36 metal-tagged antibodies was used to quantitatively analyze the TIME structure in 13 paired FLs at diagnosis and POD24.
RESULTS: Follicles and peri-follicular regions were well dissected in structure. Peri-follicular regions represented a barrier for immune infiltration into the follicles. More FL-cells in the peri-follicular regions suffered CD8+T cells attacks under simultaneous protection of regulatory T cells (Tregs) and/or macrophages compared with that in the follicles irrespective of POD24. During POD24, increased CD163- macrophages with PD-1 ligand upregulation and decreased CD8+T cells with upregulated LAG-3 expression around FL-cells were observed in the follicles. Spatial analyses demonstrated that FL-cells interacted more intimately with macrophages than with Tregs and less with cytotoxic T cells in both peri-follicular regions and follicles during POD24. In comparison, macrophages also cooperated more frequently with Tregs to simultaneously hijack FL-cells, creating an enhanced immunosuppressive environment in both peri-follicular and follicular regions during POD24.
CONCLUSIONS: Peri-follicular regions function as a barrier by recruiting both CD8+T cells and immunosuppressive cells, protecting follicular FL-cells from immune attack at diagnosis or POD24. FL-cells reside in a more immune-compromised microenvironment and evade immune cell attacks during POD24. Novel immunotherapeutic approaches harnessing LAG-3, macrophages, and Tregs will be empowered to overcome poor outcomes in patients with FL POD24.