Abstract / Summary
Abstract Primary central nervous system lymphoma (PCNSL) has significantly poorer outcomes than peripheral diffuse large B-cell lymphoma, suggesting need for novel therapies and a deeper understanding of the unique tumor immune microenvironment (TIME) within the brain. To investigate these CNS‑specific immune features, we established an orthotopic syngeneic murine PCNSL model using intracranial injection of A20 B‑cell lymphoma cells. This model showed reliable engraftment and recapitulated key pathological features of PCNSL. Compared with subcutaneous tumors, intracranial tumor‑draining lymph nodes displayed marked immunosuppression, including reduced memory CD8⁺ T-cells, impaired cytotoxicity, increased regulatory T-cells, and altered dendritic‑cell composition with expanded DC2 populations and elevated CD200 and PD‑L1. The tumor microenvironment exhibited even more pronounced dysfunction, with heightened T‑cell exhaustion and diminished CD4⁺ T‑cell activation. These findings indicate that CNS localization imposes a strongly tolerogenic immune milieu that may contribute to the inferior therapeutic responses observed in PCNSL.