Reprogramming the immune orchestra for glioblastoma: oncolytic viruses and the B-cell connection

重塑胶质母细胞瘤的免疫系统:溶瘤病毒与B细胞的联系

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Abstract

Immune checkpoint inhibitors (ICIs) are standard care for advanced non-small cell lung cancer (NSCLC), yet patients with active tuberculosis (TB) are consistently excluded from clinical trials. Furthermore, data guiding the use of dual PD-1/CTLA-4 blockade in the presence of multidrug-resistant TB (MDR-TB) is lacking. We report a 56-year-old man with stage IVA pulmonary squamous cell carcinoma (SqNSCLC) who progressed on multiple lines of therapy, including chemotherapy plus pembrolizumab, docetaxel, and the PD-1/VEGF bispecific antibody ivonescimab. During treatment, he developed secondary MDR-TB. Following stabilization with a WHO-recommended all-oral MDR-TB regimen and palliative radiotherapy for a progressive metastatic lesion, he was rechallenged with QL1706 (a unified PD-1/CTLA-4 bispecific antibody). The patient achieved sustained stable disease with a progression-free survival (PFS) of approximately 11 months. Crucially, strict multidisciplinary monitoring confirmed no TB reactivation or dissemination, and no grade ≥3 immune-related adverse events occurred. This case provides the first clinical evidence that, in carefully selected patients with controlled MDR-TB, dual checkpoint blockade with QL1706 is a feasible salvage strategy, provided that TB is rigorously managed.

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