Mass cytometric analysis of circulating immune landscape in primary central nervous system lymphoma.

Introduction: 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. Methods: 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. Results: 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). Conclusion: 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.