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. 2022 Sep 15;13:5413. doi: 10.1038/s41467-022-33116-z

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© The Author(s) 2022

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. 1 — a Volcano plot showing the hazard ratios (HR) of high/low levels of serum metabolites (n = 202, represented as points, high and low are stratified by the median of each metabolite) in CheckMate 025 renal cell carcinoma (RCC) patients with nivolumab (anti-PD1 Ab) treatment (n = 392). Overall survival is used as a Cox proportional hazards model. A cutoff at P = 0.01 is shown as a horizontal line and HR (high/low) = 1 is shown as a vertical line (HR: high/low <1 indicates that a high level of a metabolite is a benefit for ICB patients). b Kaplan–Meier plot of overall survival in RCC patients with nivolumab (anti-PD1 Ab) (High, n = 196, mean OS = 33; Low, n = 195, mean OS = 21) or everolimus (mTOR inhibitor) (High, n = 174, mean OS = 20; Low, n = 174, mean OS = 20) grouped by the inosine level at the median of baseline level. c–e Tumour volume and survival analysis of B16-F0 (c, n = 5), B16-GMCSF (d, n = 5), or 4T1 (e, n = 6) tumour-bearing mice treated with IgG2a (Ctrl), 400 mg/kg of Inosine (Ino), anti-CTLA4 + anti-PD1 (ICB) or ICB + Inosine (Ino + ICB) treatment. f tSNE plot of single-cell RNA sequencing of CD45⁺ immune cells from 4T1 tumours treated with Ctrl (n = 16199 cells) or Ino+ICB treatment (n = 9842 cells). g The frequency of gp70-specific CD8⁺ T cells in 4T1 tumour with Ctrl (n = 6), Ino (n = 6), ICB (n = 6), or Ino+ICB (n = 8) treatment for 15 days. Data are presented as Mean ± s.e.m. Statistical significance was determined by one-way ANOVA and Tukey test for multiple comparisons (tumour sized of c–e, g) or log-rank (Mantel–Cox) test (survival analysis of b–e). Source data are provided as a Source Data file.