Fig. 4: Emergence of CiMs in advanced solid cancers.

a Schematic of experimental design. b Body weight of control and 4T1 breast cancer mice (n = 8 mice per group). c Forelimb grip strength of control (n = 4 mice) and 4T1 breast cancer (n = 6 mice) mice at the endpoint. The values were normalized to those of the control group. d Skeletal muscle weights of control (n = 4 mice, at day 11 to 13) and 4T1 breast cancer (n = 6 mice, at day 11 to 13) mice. Weights are normalized to the IBW and presented as weight/100 mg IBW. e, f HE staining and CSA of quadriceps from control and 4T1 breast cancer mice (n = 3 mice per group). Representative images (e) and average (f) of CSA are shown. Scale bar, 50 μm. g mRNA expression levels of muscle atrophy markers in quadriceps from control (n = 3 mice) and 4T1 breast cancer (n = 4 mice) mice at the endpoint. Log2 fold change values compared to mean values of control are shown. h, i Flow cytometric analysis of total PB from control and 4T1 breast cancer mice (n = 8 mice per group). Representative flow cytometry plots (h) and the frequencies of CD38⁺ cells in PB Ly6C⁺ inflammatory monocytes (i) are shown. j Flow cytometric analysis of the total BM from control and 4T1 breast cancer mice (n = 8 mice per group). The frequencies of CD38⁺ cells in BM Ly6C⁺ inflammatory monocytes are shown. k Diff-Quik staining of CD38⁺ Ly6C⁺ inflammatory PB monocytes from 4T1 mice with cachexia. Scale bar, 10 μm. l Relative diameter of C2C12 myotubes after co-culture with Ly6C⁺ inflammatory monocytes from control mice or CD38⁺ Ly6C⁺ inflammatory monocytes from 4T1 breast cancer mice. Representative results from more than three independent experiments are shown. The number of muscle fibers analyzed in each sample is shown. m mRNA expression levels of Il36g in Ly6C⁺ inflammatory monocytes from control mice (n = 4 mice) and in CD38⁺ Ly6C⁺ inflammatory monocytes from 4T1 breast cancer mice (n = 5 mice). Log2 fold change values compared to mean values of control are shown. n Expression levels of neutrophil-related genes in Ly6C⁺ inflammatory monocytes from control mice (n = 4 mice) and in CD38⁺ Ly6C⁺ inflammatory monocytes from 4T1 breast cancer mice (n = 5 mice). Log2 fold change values compared to mean values of control are shown. o Schematic of experimental design. p, q Flow cytometric analysis of total PB from 4T1 breast cancer mice treated with vehicle (n = 4 mice) and TAK-242 (n = 7 mice). Representative flow cytometry plots (p) and the frequencies of CD38⁺ cells in PB Ly6C⁺ inflammatory monocytes (q) are shown. Statistical analyses were performed using a two-tailed unpaired Student’s t test. Data are presented as the mean ± SD. Source data are provided as a Source Data file.