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ORIGINAL RESEARCH article

Front. Immunol.

Sec. Comparative Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1658015

Mass Cytometric Analysis of Circulating Immune Landscape in Primary Central Nervous System Lymphoma

Provisionally accepted
Yuchen  WuYuchen Wu1Liwei  LvLiwei Lv2Jing  LiuJing Liu1Xuefei  SunXuefei Sun1Chunji  GaoChunji Gao3Shengjun  SunShengjun Sun1Nan  JiNan Ji1Wenjing  WangWenjing Wang4*Yuanbo  LiuYuanbo Liu1*
  • 1Beijing Tiantan Hospital, Capital Medical University, Beijing, China
  • 2Beijing Tongren Hospital CMU, Beijing, China
  • 3Chinese PLA General Hospital, Beijing, China
  • 4Beijing You'an Hospital Affiliated to Capital Medical University Beijing Institute of Hepatology, Beijing, China

The final, formatted version of the article will be published soon.

The peripheral immune profiles of patients with primary central nervous system lymphoma (PCNSL) remain poorly characterized. Investigating immune dysregulation in PCNSL may help elucidate the underlying disease mechanisms. We aimed to define the circulating immune landscape in PCNSL by characterizing the immune cell profiles in 16 patients and 6 healthy participants using mass cytometry. Patients exhibited significant alterations in peripheral blood mononuclear cells, including expansion of CD45RO+ classical monocytes (p=0.017), reduced intermediate subsets (p=0.01), and elevated CD38 expression (p<0.001). The number of terminally differentiated CD8+CD57+ T cells increased (p=0.013), and treatment induced effector T cell (CD8+ T effector/effector memory cells, p<0.05) expansion, accompanied by co-upregulation of CD38, HLA-DR, and CD107a (p<0.01). Patients < 60 years had higher frequencies of CD8+ naïve T cells (p<0.05), and progressive disease correlated with CD56brightNK cell accumulation (p<0.01). Therefore, the circulating immune landscape in PCNSL is characterized by skewed monocyte activation, T cell terminal exhaustion, and chemotherapy-induced effector T cell expansion. Our findings link peripheral immune features to the tumor microenvironment biology. Understanding these systemic immune alterations may provide insights into tumor immune evasion and offer a roadmap for reversing PCNSL-associated immunosuppression.

Keywords: Primary central nervous system lymphoma (PCNSL), mass cytometry, t cell exhaustion, Tumor Microenvironment, Immunosuppression

Received: 02 Jul 2025; Accepted: 10 Sep 2025.

Copyright: © 2025 Wu, Lv, Liu, Sun, Gao, Sun, Ji, Wang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Wenjing Wang, angwenjing85321@ccmu.edu.cn
Yuanbo Liu, yuanbol@ccmu.edu.cn

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