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

Journal Article (Letter)

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.

Full Text

Duke Authors

Cited Authors

  • Liu, L; Yu, X; Li, Z; He, X; Zha, J; Lin, Z; Hong, Y; Zheng, H; Lai, Q; Ding, K; Jia, X; Fu, G; Yu, H; Yang, H; Li, Z; Young, KH; Xu, B

Published Date

  • August 22, 2022

Published In

Volume / Issue

  • 15 / 1

Start / End Page

  • 115 -

PubMed ID

  • 35996180

Pubmed Central ID

  • PMC9396877

Electronic International Standard Serial Number (EISSN)

  • 1756-8722

Digital Object Identifier (DOI)

  • 10.1186/s13045-022-01326-z


  • eng

Conference Location

  • England