Fig. 1
Physical exercise “heats” immuno-cold tumors by inhibiting cholesterol synthesis. a Overview of DEGs between tumors in mice with or without voluntary wheel running. b Schematic protocol of the experimental procedures in C57BL/6 mice. c Tumor growth in Lewis carcinoma-bearing mice with or without exercise (n = 5 per group). d t-SNE plots of 50,000 cells per group colored using PhenoGraphcluster. e Immunofluorescence revealing the infiltration of CD8+ T cells and M1 macrophages, and the expression of HMGCR and SQLE. Representative images demonstrating SQLE expression in para-tumor and tumor tissues using anti-SQLE staining (f) and semi-quantitative analysis (g). h Representative images showing CD8 expression in the high- and low-SQLE groups. i Semi-quantitative analysis of the correlation between SQLE and CD8 expression. j Expression levels of SQLE in different cell types from NSCLC tissues in six scRNA-seq datasets. k and l Expression of SQLE in patients with different immunotherapy responses and ROC analysis of the predictive value of SQLE (n = 30 in the non-responder group, n = 13 in the responder group). Data obtained by merging the GSE126044 and GSE135222 datasets. m Tumor growth curve and SQLE overexpression in tumors from mice with exercise (n = 5 per group). n Representative images showing the tumors harvested from Lewis carcinoma-bearing mice (n = 5 per group). o Representative images showing the infiltration of CD8+ T cells and M1 macrophages in the above tumors. p Schematic diagram of this study: exercise heats up the TIME by suppressing SQLE expression. **P < 0.01, ***P < 0.001. MDSC myeloid-derived suppressor cell, IRS immunoreactivity score, DEGs differentially expressed genes, HMGCR 3-hydroxy-3-methylglutaryl-coenzyme A reductase, SQLE squalene epoxidase, NSCLC non-small cell lung cancer, scRNA-seq single-cell RNA sequencing, OE overexpression, TIME tumor immune microenvironment, ROC receiver operating characteristic, t-SNE t-distributed Stochastic Neighbor Embedding, DPT double positive T cells