Multimodal spatial profiling reveals distinct myeloid-defined ENKTL subgroups and tumor-myeloid cooperativity within prognostic inflammatory niche

@article{deng2026multimodal,
  title = {{Multimodal spatial profiling reveals distinct myeloid-defined ENKTL subgroups and tumor-myeloid cooperativity within prognostic inflammatory niche}},
  author = {Lichang Deng and Min Liu and Reagan Entigu Anak Linton and Kaijie Hu and Shruti Sridhar and Giorgio Bertolazzi and Sai Mun Leong and Ling-Wen Ding and Nicholas Syn and Shuangyi Fan and Cho Mar Myint Wai and Yi-Qi Li and Jin-Xin Bei and Jie Xiong and Wei-Li Zhao and Susan Swee-Shan Hue and Joe Poh Sheng Yeong and Li Yen Chong and Li-Mei Poon and Choon Kiat Ong and Jing Quan Lim and Soon Thye Lim and Jinmiao Chen and Hang Xu and Anand Devaprasath Jeyasekharan and Claudio Tripodo and Siok-Bian Ng},
  journal = {Leukemia},
  year = {2026},
  month = aug,
  doi = {10.1038/s41375-026-03118-7},
  url = {https://doi.org/10.1038/s41375-026-03118-7},
  note = {CC BY-NC-ND 4.0},
}

TY  - JOUR
TI  - Multimodal spatial profiling reveals distinct myeloid-defined ENKTL subgroups and tumor-myeloid cooperativity within prognostic inflammatory niche
AU  - Lichang Deng
AU  - Min Liu
AU  - Reagan Entigu Anak Linton
AU  - Kaijie Hu
AU  - Shruti Sridhar
AU  - Giorgio Bertolazzi
AU  - Sai Mun Leong
AU  - Ling-Wen Ding
AU  - Nicholas Syn
AU  - Shuangyi Fan
AU  - Cho Mar Myint Wai
AU  - Yi-Qi Li
AU  - Jin-Xin Bei
AU  - Jie Xiong
AU  - Wei-Li Zhao
AU  - Susan Swee-Shan Hue
AU  - Joe Poh Sheng Yeong
AU  - Li Yen Chong
AU  - Li-Mei Poon
AU  - Choon Kiat Ong
AU  - Jing Quan Lim
AU  - Soon Thye Lim
AU  - Jinmiao Chen
AU  - Hang Xu
AU  - Anand Devaprasath Jeyasekharan
AU  - Claudio Tripodo
AU  - Siok-Bian Ng
PY  - 2026
DA  - 2026/08/24
JO  - Leukemia
DO  - 10.1038/s41375-026-03118-7
UR  - https://doi.org/10.1038/s41375-026-03118-7
AB  - Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive Epstein–Barr virus (EBV)-associated malignancy with a heterogeneous tumor microenvironment, yet macrophage heterogeneity and tumor-macrophage crosstalk remain poorly defined. Here, we integrate spatial transcriptomic and proteomic profiling with single-cell spatial molecular imaging of ENKTL samples and identify two subgroups defined by distinct macrophage programs. Subgroup 1 is enriched for inflammatory macrophages exhibiting IFN-α/γ responses and immune-regulatory molecules including IDO1 and CD274, whereas Subgroup 2 is immune-quiescent and macrophage-sparse, with its macrophage compartment skewed towards STAB1 macrophages with scavenging features. Notably, an NF-κB-activated and EBV-associated tumor subset is specifically enriched in Subgroup 1, displaying concurrent immunostimulatory and immunoregulatory features that parallel the co-enriched myeloid states and showing reproducible sample-level associations with these myeloid states across datasets. Spatial neighborhood analysis further delineates an inflammation niche where NF-κB tumor cells physically co-localize with these inflammatory macrophages, accompanied by enhanced tumor-myeloid and myeloid-myeloid signaling, implicating a process of tumor-associated myeloid recruitment followed by CCL- and IL1-mediated myeloid self-reinforcement. Critically, higher abundance of this niche correlates with improved survival across independent cohorts, revealing contrasting spatial tumor-immune architectures with prognostic relevance. Together, our study provides a spatially resolved framework for understanding ENKTL biology and guiding immunotherapeutic strategies.
SN  - 0887-6924
SN  - 1476-5551
ER  -