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Shiqiang Wang,1,2 Chongling Hu,2 Fei Xie,3 Yanhui Liu1 1Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, People’s Republic of China; 2Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, People’s Republic of China; 3Department of Neurosurgery, Ziyang First People’s Hospital, Ziyang 641300, People’s Republic of ChinaCorrespondence: Yanhui LiuDepartment of Neurosurgery, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou Zone, Chengdu 610041, People’s Republic of ChinaEmail liuyanhuicd@163.comAbstract: The central nervous system (CNS) is regarded as an immune privileged environment; however, changes in the neuroimmunology paradigm have led to an increased interest in systematic immunotherapy in lung cancer therapy. The presence of the lymphatic system in the CNS as well as the physiological and biochemical changes in the blood–brain barrier in the tumor microenvironment suggests that immunocytes are fully capable of entering and exiting the CNS. Emerging clinical data suggest that inhibitors of programmed death receptor-1/programmed death ligand 1 (PD-1/PD-L1) can stimulate surrounding T cells and thus have antitumor effects in the CNS. For example, PD-1 antibody (pembrolizumab) monotherapy has displayed a 20– 30% encephalic response rate in patients with brain metastases from malignant melanoma or non-small cell lung cancer. Combined application of nivolumab and ipilimumab anti-PD-1 and anti-cytotoxic T-lymphocyte-associated protein 4 showed an encephalic response rate of 55% in patients with brain metastases of melanoma. Further evidence is required to verify these response rates and identify the mechanisms of curative effects and drug tolerance. While regional treatments such as whole-brain radiosurgery, stereotactic radiosurgery, and brain