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. 2020 Oct 15;21:263. doi: 10.1186/s13059-020-02166-1

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© The Author(s) 2020

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — Performance of biomarkers is incoherent across different ICB clinical cohorts. a CD274 level significantly correlates with ICB response in Gide et al., but not the other studies. b Tumor mutation burden significantly correlates with ICB response in the Mariathasan et al. study, but not in the Hugo et al. or Snyder et al. studies (boxplot shows the minimum, first quartile, median, third quartile, and maximum values of each group; n.s., not significant; **P < 0.01, ***P < 0.001; Student’s t test with Benjamini-Hochberg adjustment of P values for multiple comparison). c Systematic evaluation of multiple biomarkers of ICB response in different clinical cohorts reveals inconsistent performance. d Two non-mutually exclusive models can explain the inconsistent performance of biomarkers in different clinical cohorts. Model 1 assumes that different mutation profiles and epigenetic status of cancer cells from different tumors (colored dots) determine the heterogeneous response (size of dots) after ICB treatment (syringe). Model 2 assumes that host-specific factors determine response