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. 2022 Mar 29;13:852811. doi: 10.3389/fimmu.2022.852811

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Copyright © 2022 Yang, Xing and Sun

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Potential mechanisms that NSCLC patients with brain metastases could benefit from ICIs. (1) BBB will be loosened with the progression of BMs. (2) Immune cells and tumor-associated antigen could be transported between intracranial and peripheral environments by meningeal lymph-vessels. (3) Part of ICI mAbs can enter the intracranial environment and be detected. (4) BBB can get loose due to broken tight conjunction and enhanced trans-endothelial migration through the up-regulation of adhesins and chemokines mediated by INF-γ inducing T-cell- secreted INF-γ. (6)(7)(8) ICIs revive anti-tumor immune in lymph nodes, primary disease and peripheral circulation. ICI, immune checkpoint inhibitor; RT, radiotherapy; CT, chemotherapy; IFN, interferon; BBB, blood-brain barrier; mAb, monoclonal antibody; IFN, interferon.