Immunotherapy is dramatically changing the therapeutic landscape of advanced Non Small Cell Lung Cancer (NSCLC), with unprecedented results compared with chemotherapy. However, this novel treatment approach poses several novel challenges, including optimal treatment duration, coexistence with other conventional therapies (radiotherapy, targeted therapies, and chemotherapy), and activity in special populations, including patients with brain metastases (BMs). Traditionally, central nervous system

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... (CNS) has been considered an immune-privileged organ, although recent evidences suggest a potential role of the immune system as exploitable target for cancer immunotherapy. Here we present a case of a non-squamous NSCLC patient with a rapid and long-lasting response to the anti-PD1 agent Nivolumab with a remarkable activity in the CNS, without previous brain irradiation.