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. 2019 Apr 2;10:1492. doi: 10.1038/s41467-019-09525-y

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© The Author(s) 2019

Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 7 — Altered UPR in melanoma responders of anti-CTLA-4 immune therapy. a Analysis of ER stress markers genes in non-responders (NR) (n = 16) and responders (R) (n = 14) to immune checkpoint therapy in melanoma samples from MGH/DFCC (USA). b Analysis of ER stress markers genes in NR (n = 16) and R (n = 9) to anti-CTLA-4 immunotherapy in melanoma samples from Zurich Hospital (Switzerland). c Kaplan–Meier curves for progression-free survival probability in melanoma patients demonstrating low (n = 15 patients) versus high sXBP1(n = 14 patients) in tumor specimens obtained before immune checkpoint therapy at MGH/DFCC. d Kaplan–Meier estimates of progression-free survival probability in melanoma patients demonstrating low (n = 14 patients) versus high ATF4 (n = 16 patients) in tumor specimens obtained before immune checkpoint therapy in melanoma samples at MGH/DFCC. e Representative micrographs of IHC staining of BiP after anti-PD-1 immunotherapy in melanoma samples obtained at Rambam Health Care Center (Israel) (scale bar = 25 μm). f IHC score of BiP staining in NR (n = 10) and R (n = 11) to anti-PD-1 immunotherapy in melanoma samples from Rambam Health Care Center (Israel). g, h Kaplan–Meier estimates of (g) overall survival and (h) disease-free survival probability in melanoma patients demonstrating low (<25%, n = 12 patients) versus high melanoma cell expression of BiP (>25%, n = 9 patients) in tumor biospecimens obtained before initiation of systemic anti-PD-1 antibody treatment in melanoma samples from Rambam Health Care Center (Israel). i IHC staining of BiP in melanoma samples from select patients prior to, on and after immunotherapy treatment from MGH/DFCC (USA). Scale bar = 50 μm. Graphs show the mean ± s.e.m. *P < 0.05, **P < 0.005, ***P < 0.001, ****P < 0.0001 by two-tailed t-test or Mann–Whitney U test (a, b, f) or log-rank test (c, d, g, h)