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1621 CD163+ Macrophages Orchestrate Tumor Immunity By Spatially Fortifying Follicular Lymphoma Against CD8+ T Cells Attack during Early Progression

Program: Oral and Poster Abstracts
Session: 622. Lymphomas: Translational – Non-Genetic: Poster I
Hematology Disease Topics & Pathways:
Research, Translational Research
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Zhijuan Lin, MD1*, Xingxing Yu2*, Yan Hong2*, Long Liu2*, Zhifeng Li2*, Jie Zha2* and Bing Xu2

1Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, China
2Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, School of Medicine, Xiamen University, Xiamen, Fujian, China

Background: The tumor immune microenvironment (TIME) plays a pivotal role in the development and progression of follicular lymphoma (FL). However, the evolution of TIME during progression of disease within 24 months (POD24) remains poorly understood.

Methods: We employed imaging mass cytometry with a panel of 36 meta-tagged antibodies to examine the immune architecture of lymph nodes from 13 FL patients, both at diagnosis and during POD24.

Results: Our analysis revealed a decrease in immune infiltration from the peri-follicular regions towards the follicular centers in FL. Notably, there was an increase in CD163+ macrophages within the follicles, accompanied by an upregulation of PD-1 ligands during POD24. Spatial analysis showed that FL cells tend to evade immune attacks not merely through spatial separation from CD8+ T cells but by proactively recruiting immunosuppressive cells prior to encountering these T cells. Furthermore, during POD24, more CD8+ T cells in proximity to FL cells were found interacting with macrophages rather than regulatory T cells (Tregs). There was also an observed increase in the cooperation between macrophages and Tregs, which collectively worked to subdue cytotoxic T cell activity, thereby creating a more immunosuppressed environment.

Conclusions: FL cells exhibit more aggressive evasion tactics and exist within a more immunosuppressive microenvironment during POD24. These findings suggest that immunotherapeutic strategies targeting PD-1, macrophages, and CTLA-4 may hold promise for improving outcomes in FL patients experiencing early progression.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH