a, Volcano plot showing differentially expressed genes between tumour CXCL13+BHLHE40+ TH1-like T cells (n = 203) and other TH cells in tumours (n = 723; Supplementary Table 10). Adjusted P < 0.01 (two-sided unpaired limma-moderated t-test; Benjamini–Hochberg adjusted P value) and fold change ≥ 2. b, Venn diagram showing the overlap of tumour CD8+ exhaustion-related genes identified in this study (n = 68, Supplementary Table 11) with those from previous melanoma8 (n = 349), HCC9 (n = 82) and NSCLC10 (n = 90) studies. The detailed overlaps of CD8+ exhaustion-related genes in different cancer types are in Supplementary Table 11. P < 2.2 × 10−16, hypergeometric test. c, CD4+ naive (TN) and memory (TMEM) T cells were gated as CD45RA+CCR7+ and CD45RA−CCR7+/− cells by FACS. d, FACS plots of IGFLR1 expression in activated CD4+ T cells (n = 6 donors, n = 3 independent experiments). e, Quantification of IGFLR1 expression levels from d as a percentage of IGFLR1+ TN or TMEM CD4+ subsets under suboptimal activation conditions (n = 7). Each symbol represents a donor with mean ± s.e.m. shown (e, l). f, Representative FACS plots for HAVCR2 and IFNγ expression levels in CD8+ Tconv (activated by anti-CD3 plus anti-CD28) and TCS cells (in vitro chronically stimulated exhausted CD8+ T cells from corresponding individuals). Numbers in quadrants indicate the percentage of positive cells (n = 5 donors, n = 2 independent experiments). g, Representative histograms of PD-1, HAVCR2 (n = 8 donors, n = 3 independent experiments), CD39 and LAG3 (n = 4 donors, n = 2 independent experiments) expression levels in CD8+ Tconv and TCS cells. h, Quantification of IFNγ levels produced by CD8+ Tconv and TEX cells from g of three donors. i, Representative histogram of IGFLR1 expression levels in CD8+ Tconv and TCS cells. j, Expression levels of IGFLR1 in activated CD8+ Tconv and TCS cells determined by FACS (MFI, mean fluorescent intensity; n = 6 donors, n = 4 independent experiments). k, Representative histograms of HAVCR2 expression in TCS cells subjected to re-stimulation with anti-CD3 alone (control) or together with recombinant human IGFL3 as well as indicated antibodies for 2 days (n = 5 donors, n = 3 independent experiments). l, Quantification of HAVCR2 levels from k. Two-sided paired Student’s t-test (e, j and l).