CELL INTELLIGENCE · 肿瘤细胞治疗研究

OBJECTIVES: Leptomeningeal metastasis (LM) is a serious complication of advanced non-small-cell lung cancer (NSCLC). Intrathecal administration of nivolumab or interleukin-2 (IL-2) has demonstrated efficacy in this setting. Preclinical and limited clinical evidence suggest that combining IL-2 with anti-PD1 therapy may synergistically enhance anti-tumor immunity. However, clinical data on the efficacy and safety of intrathecal co-administration of nivolumab and IL-2 are lacking. MATERIALS AND METHODS: We describe a case of NSCLC with LM, refractory to multiple EGFR tyrosine kinase inhibitors and previous intrathecal therapies, treated with intrathecal nivolumab and IL-2. Single-cell RNA sequencing (scRNA-seq) was performed on cerebrospinal fluid (CSF) samples collected before and after treatment. RESULTS: This is the first reported case of intrathecal nivolumab plus IL-2 in NSCLC with LM resistant to standard systemic and intrathecal therapies. The patient experienced marked clinical improvement, including substantial remission of intracranial metastases, neurological symptom relief, and a reduction in tumor marker levels, without notable treatment-related adverse events. scRNA-seq analysis of CSF revealed a post-treatment decrease in malignant cell populations and a concomitant increase in immune effector cells, particularly CD8 + T cells and NK cells. Malignant cells exhibited upregulated antigen presentation and apoptosis. Cell-cell interaction analysis indicated enhanced NK cell-mediated cytotoxicity via FASL-FAS signaling and reduced immunosuppressive interactions between regulatory CD4 + T cells and effector memory CD8 + T cells. CONCLUSIONS: This case report provides preliminary evidence supporting the feasibility, safety, and potential efficacy of intrathecal nivolumab and IL-2 in treating NSCLC-associated LM. These findings warrant further investigation in prospective clinical studies.