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. 2019 Mar 18;10:491. doi: 10.3389/fimmu.2019.00491

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Copyright © 2019 Guram, Kim, Wu, Sanders, Patel, Schoenberger, Cohen, Chen and Sharabi.

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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A threshold model for immune activation. (A) Checkpoint Blockade Immunotherapy (CBI) lowers the threshold for immune activation but not enough to trigger an immune response. (B) CBI lowers the threshold for immune activation to trigger an anti-tumor immune response but not an auto-immune response. (C) Baseline immunity to self antigens is higher than immunity to tumor associated antigens. CBI lowers the threshold to induce an auto-immune response but no anti-tumor immune response or immune-related adverse event. (D) Single agent or dual agent CBI lowers the threshold for immune activation to trigger an anti-tumor immune response and an auto-immune response or immune-related adverse event.