IMMU-02. INTRACRANIAL PROGRESSION IS LESS COMMON IN PATIENTS WITH ADVANCED NSCLC RECEIVING CANCER IMMUNOTHERAPY

Abstract BACKGROUND Intracranial metastases are common in patients with non-small cell lung cancer (NSCLC) and their prognosis is very poor. Furthermore, intracranial progression is common during systemic therapy due to the inability to cross the blood brain barrier, but the impact of cancer immunotherapy on intracranial progression remains unclear. METHODS We analyzed clinical data to evaluate the frequency of intracranial progression in patients with advanced NSCLC treated with PD-1 blockade therapies compared to patients not treated with PD-1 blockade therapies (Approval number: 2201-022). We also evaluated durable responses to PD-1 blockade and analyzed tumor-infiltrating lymphocytes using tumor-rechallenging murine models. RESULTS The clinical data analysis showed that the frequency of intracranial progression was significantly lower in patients with advanced NSCLC treated with PD-1 blockade than in patients treated with cytotoxic chemotherapy. In murine models, intracranial rechallenged tumors after initial rejection by PD-1 blockade therapy were suppressed, as observed for subcutaneous tumors. Accordingly, PD-1 blockade increased long-lived memory precursor effector T cells and antigen-specific T cells in intracranial lesions. In contrast, intracranial rechallenged different tumors were not suppressed. CONCLUSIONS The CNS has been considered a site in which cancer patients tend to experience progression during systemic therapies, however our results indicate that cancer immunotherapies can prevent intracranial progression, maintaining long-term effects intracranially as well as systemically. (Kemmotsu N. et. al., Int J Cancer, 2024)