Extended Data Fig. 4: Methionine supplementation promotes T cell anti-tumour immunity.

a, b, H3K79me2 (a) and STAT5 (b) levels in CD8⁺ T cells from tumour draining lymph node and tumour in B16F10 bearing mice. c, d, H3K79me2 (c) and STAT5 (d) levels in CD8⁺ T cells from spleen and tumour ascites in ID8 bearing mice. e, H3K79me2 levels in CD8⁺ T cells from healthy peripheral blood and human ovarian cancers ascites. f, g, H3K79me2 (f) and STAT5 (g) levels in CD8⁺ T cells from healthy human blood and human ovarian cancer omentum tissues. h, i, FACS showed H3K79me2 and STAT5 levels in human tumour infiltrating CD8⁺ T cells. j–m, Effect of methionine on human tumour infiltrating CD8⁺ T cells. Human colorectal cancer infiltrating CD8⁺ T cells were cultured with or without methionine. T cell cytokine production (j, k), H3K79me2 (l), and STAT5 (m) were analysed by FACS. One representative of four is shown. n, Effect of methionine supplementation on apoptosis of tumour infiltrating CD8⁺ T cells and ID8 tumour cells in vivo. ID8 tumour bearing mice were treated with methionine or PBS. T cell and tumour cell apoptosis was determined by FACS. o, Methionine levels in ID8 tumour after methionine or PBS treatment. p–r, Effect of anti-PD-L1 on methionine-affected CT26 tumour progression. Mice bearing CT26 tumour were treated with anti-PD-L1, methionine, and their combination. Tumour volume (p), T cell tumour infiltration (q) and apoptosis (r) were assessed. Data are mean ± s.e.m. Information on sample sizes, experimental number, times, biological replicates, statistical tests, and P values is available in ‘Statistics and reproducibility’.

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