Dataset Information

Revealing the evolution of the tumor immune microenvironment in follicular lymphoma patients progressing within 24 months using single-cell imaging mass cytometry.

ABSTRACT:

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.

SUBMITTER: Liu L

PROVIDER: S-EPMC9396877 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Revealing the evolution of the tumor immune microenvironment in follicular lymphoma patients progressing within 24 months using single-cell imaging mass cytometry.

Liu Long L Yu Xingxing X Li Zhifeng Z He Xiaohua X Zha Jie J Lin Zhijuan Z Hong Yan Y Zheng Huijian H Lai Qian Q Ding Kaiyang K Jia Xian X Fu Guo G Yu Haifeng H Yang Haiyan H Li Zhiming Z Young Ken H KH Xu Bing B

Journal of hematology & oncology 20220822 1

<h4>Background</h4>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.<h4>Methods</h4>Spatially resolved and single-cell image mass cytometry with a panel of 36 metal-tagged antibodies was used to quantitatively ana ...[more]

PMID: 35996180

Similar Datasets

Project description:ObjectiveFollicular lymphoma (FL) occurring progression within 24 months (POD24) after initial immunochemotherapy has poor prognosis. GLUT1 affects glycolysis within tumor microenvironment (TME) and promotes tumor progression. However, its specific mediated mechanism remains unclear in FL.MethodsBaseline GLUT1 expression, infiltrations of M2 macrophage, and CD8+ T-cells were assessed by immunohistochemistry in FL with POD24 and long-term remission respectively. The spatial features of TME were assessed by MIBI-TOF and proteomics. Predictive immunophenotypes for POD24 occurrence was analyzed by random forest algorithm. The lactate production and the induction of M2 macrophages were detected when GLUT1 was transfected or knocked down in DOHH2. The activation of PI3K/Akt/mTOR signaling in DOHH2 and WSU-FSCCL cells co-cultured with induced inhibitory immunocytes was tracked by western blotting.ResultsThe FL with POD24 exhibited higher baseline GLUT1 expression and increased infiltration of various inhibitory immunocytes. Spatial signatures of 69 immunophenotypes could predict POD24 occurrence. The activation of PI3K/ Akt /mTOR signaling pathway was not significant in both groups. The supernatant of DOHH2-GLUT1 cells which had more lactate content could induce more M2-type macrophages than that of DOHH2/siRNA GLUT1 cells. When co-cultured with exhausted CD8+ T cells, M2-type macrophages and Tregs, compared with WSU-FSCCL cells, DOHH2 cells with high GLUT1 expression induced more M2-type macrophages and was triggered activation of PI3K/ Akt /mTOR signaling pathway.ConclusionTumor cells overexpressing GLUT1 could domesticate immunocytes to form an immunosuppressive TME, which promotes occurrence of POD24 and gradually activates PI3K/ Akt /mTOR pathway of tumor cells in FL.SignificanceTumor cells overexpressing GLUT1 could domesticate immunocytes to form an immunosuppressive microenvironment, which in turn promoted the growth of tumor cells and was related to the progression of disease within 24 months in FL. Suppressive immunocytes gradually activated PI3K/ Akt /mTOR pathway of tumor cells in later stage. Distinguishing spatial features of immunocytes could well predict POD24 occurrence, hoping to benefit these patients from early anti-metabolism therapy based on GLUT1 in the future.

Dataset Information

Revealing the evolution of the tumor immune microenvironment in follicular lymphoma patients progressing within 24 months using single-cell imaging mass cytometry.

Background

Methods

Results

Conclusions

Publications

Revealing the evolution of the tumor immune microenvironment in follicular lymphoma patients progressing within 24 months using single-cell imaging mass cytometry.

Similar Datasets

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