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. 2020 Feb 2;9(1):1722023. doi: 10.1080/2162402X.2020.1722023

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© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Figure 4. — Clustering of patients with any grade irAEs based on peripheral blood T-cell parameters.

(A) Unsupervised hierarchical clustering using five T-cell parameters (eTreg_post/pre, Th17/Th1_pre, Ki-67_post, CD4TNF_post, and CD8TNF_post) in the 45 patients with any grade irAEs (1 patient/row). The z-scores are column normalized. Patients with grade 1/2 irAEs are indicated in blue and patients with grade ≥3 irAEs are indicated in red. Patients were clustered into four subgroups; TNF-related, Th17-related, CD8-related Treg compensated, and CD8-related Treg non-compensated. (B) CD4TNF_post or CD8TNF_post in patients with no irAE (n = 46), other irAEs (Th17-related and CD8-related; n = 22), and TNF-related irAEs (n = 23). (C) Th17/Th1_pre in patients with no irAE (n = 46), other irAEs (TNF-related and CD8-related; n = 39), and Th17-related irAEs (n = 6). (D-F) Ki-67_post (D), eTreg_post/pre (E), ratio of Ki-67_post and eTreg_post/pre (Ki-67_post/eTreg_post/pre) (F), in patients with no irAE (n = 46), other irAEs (TNF-related and Th17-related; n = 29), CD8-related Treg-compensated (n = 11), and CD8-related Treg-uncompensated irAEs (n = 7). Error bars indicate standard deviation of the mean. Statistical analyses were performed using Kruskal–Wallis test and post-hoc analysis by Dunn’s test (B-F). *P < .05, **P < .01, ***P < .001, ****P < .0001.